bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dengue after Zika: characterizing impacts of Zika emergence on endemic dengue transmission
Authors: Borchering Rebecca K. , Huang Angkana , Mier-y-Teran-Romero Luis , Rojas Diana P. , Rodriguez-Barraquer Isabel , Katzelnick Leah C. , Martinez Silvio D. , King Gregory D. , Cinkovich Stephanie C. , Lessler Justin , Cummings Derek A.T. 
Published: March 2019

AbstractIn 2015 and 2016, Zika virus (ZIKV) swept through many Latin American countries where dengue virus (DENV) is endemic. Dengue and Zika viruses are of the same family, share a vector and may interact competitively or synergistically through human immune responses. We examine dengue incidence data from Brazil and Colombia from before, during, and after the Zika epidemic. We find evidence that dengue incidence was atypically low in 2017 in both Brazil and Colombia. We investigate whether Zika incidence at the state or department level is associated with changes in dengue incidence and find mixed results. We use simulations to investigate expected impact of cross-protection or enhancement between dengue and Zika. Our simulations show that regardless of the mechanism, low periods of dengue incidence are followed by a resurgence in dengue cases. It is therefore likely that countries currently experiencing low levels of dengue incidence will experience large dengue seasons in the near future. By considering multiple combinations of DENV and ZIKV reproduction numbers, we demonstrate that the mixed results of our statistical models are not entirely unexpected. Correlations in DENV and ZIKV reproduction number could contribute to complicating or masking an association between their case counts.
Trajectories of change after a health-education program in Japan
Authors: Park MJ , Green Joseph , Jung Hun Sik , Park Yoon Soo 
Published: March 2019

ABSTRACTBackgroundHealth education can benefit people with chronic diseases. However, in previous research those benefits were small, and reinforcement to maintain them was not effective. A possible explanation is that the benefitsappearedto be small and reinforcementappearedto be ineffective because those analyses mixed data from two latent groups: one group of people who needed reinforcement and one group of people who did not. The hypothesis is that mixing the data from those two different groups caused the true effects to be “diluted.”MethodsTo test that hypothesis we used data from the Chronic Disease Self-Management Program in Japan, focusing on anxiety, depression, and patient-physician communication. To identify latent trajectories of change after the program, we used growth-mixture modeling. Then, to find out which baseline factors were associated with trajectory-group membership, we used logistic regression.ResultsGrowth-mixture modeling revealed two trajectories – two groups that were defined by distinct patterns of change after the program. One of those patterns was improvement followed by backsliding: decay of impact. On anxiety and depression the decay of impact was large enough to be clinically important, and its prevalence was as high as 50%. Next, logistic regression analysis revealed that being in the decay-of-impact group could be predicted from multimorbidity, low self-efficacy, and high scores on anxiety or depression at baseline. In addition, one unexpected finding was an association between multimorbidity andbetterpatient-physician communication.ConclusionsThese results support the hypothesis that previous findings (i.e.apparentlysmall effect sizes andapparentlyineffective reinforcement) actually reflect “dilution” of large effects, which was caused by mixing of data from distinct groups. Specifically, there was one group with decay of impact and one without. Thus, evaluations of health education should include analyses of trajectory-defined groups. These results show how the group of people who are most likely to need reinforcement can be identified even before the educational program begins. Extra attention and reinforcement can then be tailored. They can be focused specifically to benefit the people with the greatest need.
Correlations between stochastic endemic infection in multiple interacting subpopulations
Authors: Meakin Sophie R , Keeling Matt J 
Published: March 2019

AbstractHeterogeneity plays an important role in the emergence, persistence and control of infectious diseases. Metapopulation models are often used to describe spatial heterogeneity, and the transition from random-to heterogeneous-mixing is made by incorporating the interaction, or coupling, within and between subpopulations. However, such couplings are difficult to measure explicitly; instead, their action through the correlations between subpopulations is often all that can be observed. We use moment-closure methods to investigate how the coupling and resulting correlation are related, considering systems of multiple identical interacting populations on highly symmetric complex networks: the complete network, thek-regular tree network, and the star network. We show that the correlation between the prevalence of infection takes a relatively simple form and can be written in terms of the coupling, network parameters and epidemiological parameters only. These results provide insight into the effect of metapopulation network structure on endemic disease dynamics, and suggest that detailed case-reporting data alone may be sufficient to infer the strength of between population interaction and hence lead to more accurate mathematical descriptions of infectious disease behaviour.
CHIME: CMOS-hosted in-vivo microelectrodes for massively scalable neuronal recordings
Authors: Kollo Mihaly , Racz Romeo R , Hanna Mina-Elraheb S , Obaid Abdulmalik M , Angle Matthew R , Wray William , Kong Yifan , Hierlemann Andreas , Müller Jan , Melosh Nicholas A , Schaefer Andreas T 
Published: March 2019

SummaryMammalian brains consist of 10s of millions to 100s of billions of neurons operating at millisecond time scales, of which current recording techniques only capture a tiny fraction. Recording techniques capable of sampling neural activity at such temporal resolution have been difficult to scale: The most intensively studied mammalian neuronal networks, such as the neocortex, show layered architecture, where the optimal recording technology samples densely over large areas. However, the need for application-specific designs as well as the mismatch between the threedimensional architecture of the brain and largely two-dimensional microfabrication techniques profoundly limits both neurophysiological research and neural prosthetics.Here, we propose a novel strategy for scalable neuronal recording by combining bundles of glass-ensheathed microwires with large-scale amplifier arrays derived from commercial CMOS of in-vitro MEA systems or high-speed infrared cameras. High signal-to-noise ratio (<20 μV RMS noise floor, SNR up to 25) is achieved due to the high conductivity of core metals in glass-ensheathed microwires allowing for ultrathin metal cores (down to <1 μm) and negligible stray capacitance. Multi-step electrochemical modification of the tip enables ultra-low access impedance with minimal geometric area and largely independent of core diameter. We show that microwire size can be reduced to virtually eliminate damage to the blood-brain-barrier upon insertion and demonstrate that microwire arrays can stably record single unit activity.Combining microwire bundles and CMOS arrays allows for a highly scalable neuronal recording approach, linking the progress of electrical neuronal recording to the rapid scaling of silicon microfabrication. The modular design of the system allows for custom arrangement of recording sites. Our approach of employing bundles of minimally invasive, highly insulated and functionalized microwires to lift a 2-dimensional CMOS architecture into the 3rd dimension can be translated to other CMOS arrays such as electrical stimulation devices.
Few Effects of a 5-week Computerized Cognitive Training Program in Healthy Older Adults
Authors: Rabipour Sheida , Morrison Cassandra , Crompton Jessica , Petrucelli Marcelo , de Oliveira Gonçalves Germano Murillo , Popescu Anita , Davidson Patrick S. R. 
Published: March 2019

AbstractComputerized cognitive training programs are becoming increasingly popular and practical for cognitive aging. Nevertheless, basic questions remain about the benefits of such programs, and about the degree to which participant expectations might influence training and transfer. Here we examined a commercial cognitive training program (Activate) in a 5-week double-blind, pseudo-randomized placebo-controlled trial. Based on a priori power analysis, we recruited 99 healthy older adults 59-91 years of age (M = 68.87, SD = 6.31; 69 women), assigning them to either the intervention or an active control program (Sudoku and n-back working memory exercises). We subdivided both groups into high and low expectation priming conditions, to probe for effects of participants’ expectations on training and transfer. We assessed transfer using a battery of standard neuropsychological and psychosocial measures that had been agreed to by the training program developers. We planned and pre-registered our analyses (on osf.io). The majority (88%) of participants progressed through the training, and most provided positive feedback about it. Similarly, the majority (80%) of participants believed they were truly training their brains. Yet, transfer of training was minimal. Also minimal were any effects of expectations on training and transfer, although participants who received high expectation priming tended to engage more with their assigned program overall. Our findings suggest limited benefits ofActivatetraining on cognition and psychosocial wellbeing in healthy older adults, at least under the conditions we used.
Selective Liposomal Transport Through Blood Brain Barrier Disruption in Ischaemic Stroke Reveals Two Distinct Therapeutic Opportunities
Authors: Al-Ahmady Zahraa S. , Jasim Dhifaf , Ahmad Sabahuddin Syed , Wong Raymond , Haley Michael , Coutts Graham , Schiessl Ingo , Allan Stuart M. , Kostarelos Kostas 
Published: March 2019

AbstractThe development of new therapies for stroke continues to face repeated translational failures. Brain endothelial cells form paracellular and transcellular barriers to many blood-borne therapies and the development of efficient delivery strategies is highly warranted. Here, in a mouse model of stroke, we show selective recruitment of clinically used liposomes into the ischaemic brain that correlates with biphasic blood brain barrier (BBB) breakdown. Intravenous administration of liposomes into mice exposed to transient middle cerebral artery occlusion took place at early (0.5h and 4h) and delayed (24h and 48h) timepoints, covering different phases of BBB disruption after stroke. Using a combination of in vivo real-time imaging and histological analysis we show that selective liposomal brain accumulation coincides with biphasic enhancement in transcellular transport followed by a delayed impairment to the paracellular barrier. This process precedes neurological damage in the acute phase and maintains long-term liposomal co-localisation within the neurovascular unit, which could have great potential for neuroprotection. Levels of liposomal uptake by glial cells are similarly selectively enhanced in the ischaemic region late after experimental stroke (2-3 days), highlighting their potential for blocking delayed inflammatory responses or shifting the polarization of microglia/macrophages towards brain repair.These findings demonstrate the capability of liposomes to maximise selective translocation into the brain after stroke and identify for the first time two windows for therapeutic manipulation. This emphasizes the benefits of selective drug delivery for efficient tailoring of new stroke treatments.
Bicarbonate Resensitization of Methicillin-ResistantStaphylococcus aureusto β-Lactam Antibiotics
Authors: Ersoy Selvi C. , Abdelhady Wessam , Li Liang , Chambers Henry F. , Xiong Yan Q. , Bayer Arnold S. 
Published: March 2019

ABSTRACTEndovascular infections caused by methicillin-resistantStaphylococcus aureus(MRSA) are a major healthcare concern, especially infective endocarditis (IE). Standard antimicrobial susceptibility testing (AST) defines most MRSA strains as ‘resistant’ to β-lactams, often leading to use of costly and/or toxic treatment regimens. In this investigation, five prototype MRSA strains, representing the range of genotypes in current clinical circulation, were studied. We identified two distinct MRSA phenotypes upon AST using standard media, with or without sodium bicarbonate (NaHCO3) supplementation: one highly susceptible to the anti-staphylococcal β-lactams, oxacillin and cefazolin (‘NaHCO3-responsive’) and one resistant to such agents (‘NaHCO3-nonresponsive’). These phenotypes accurately predicted clearance profiles of MRSA from target tissues in experimental MRSA IE treated with each β-lactam. Mechanistically, NaHCO3reduced expression of two key genes involved in the MRSA phenotype,mecAandsarA,leading to decreased production of penicillin-binding protein (PBP) 2a (that mediates methicillin resistance), in NaHCO3-responsive (but not in NaHCO3-nonresponsive) strains. Moreover, both cefazolin and oxacillin synergistically killed NaHCO3-responsive strains in the presence of the host defense antimicrobial peptide (LL-37) in NaHCO3-supplemented media. These findings suggest that AST of MRSA strains in NaHCO3-containing media may potentially identify infections caused by NaHCO3-responsive strains that are appropriate for β-lactam therapy.
Pulcherrimin formation controls growth arrest of theBacillus subtilisbiofilm
Authors: Arnaouteli Sofia , Matoz-Fernandez Daniel , Porter Michael , Kalamara Margarita , Abbott James , MacPhee Cait E. , Davidson Fordyce A. , Stanley-Wall Nicola R. 
Published: March 2019

AbstractBiofilm formation byBacillus subtilisis a communal process that culminates in the formation of architecturally complex multicellular communities. Here we reveal that the transition of the biofilm into a non-expanding phase constitutes a distinct step in the process of biofilm development. Using genetic analysis we show thatB. subtilisstrains lacking the ability to synthesize pulcherriminic acid form biofilms that sustain the expansion phase, thereby linking pulcherriminic acid to growth arrest. However, production of pulcherriminic acid is not sufficient to block expansion of the biofilm. It needs to be secreted into the extracellular environment where it chelates Fe3+from the growth medium in a non-enzymatic reaction. Utilizing mathematical modelling and a series of experimental methodologies we show that when the level of freely available iron in the environment drops below a critical threshold, expansion of the biofilm stops. Bioinformatics analysis allows us to identify the genes required for pulcherriminic acid synthesis in other Firmicutes but the patchwork presence both within and across closely related species suggests loss of these genes through multiple independent recombination events. The seemingly counterintuitive self-restriction of growth led us to explore if there were any benefits associated pulcherriminic acid production. We identified that pulcherriminic acid producers can prevent invasion from neighbouring communities through the generation of an “iron free” zone thereby addressing the paradox of pulcherriminic acid production byB. subtilis.SignificanceUnderstanding the processes that underpin the mechanism of biofilm formation, dispersal, and inhibition are critical to allow exploitation and to understand how microbes thrive in the environment. Here, we reveal that the formation of an extracellular iron chelate restricts the expansion of a biofilm. The countering benefit to self-restriction of growth is protection of an environmental niche. These findings highlight the complex options and outcomes that bacteria need to balance in order to modulate their local environment to maximise colonisation, and therefore survival.
Altered structural brain asymmetry in autism spectrum disorder: large-scale analysis via the ENIGMA Consortium
Authors: Postema Merel C. , van Rooij Daan , Anagnostou Evdokia , Arango Celso , Auzias Guillaume , Behrmann Marlene , Filho Geraldo Busatto , Calderoni Sara , Calvo Rossa , Daly Eileen , Deruelle Christine , Di Martino Adriana , Dinstein Ilan , Duran Fabio Luis S. , Durston Sarah , Ecker Christine , Ehrlich Stefan , Fair Damien , Fedor Jennifer , Feng Xin , Fitzgerald Jackie , Floris Dorothea L. , Freitag Christine M. , Gallagher Louise , Glahn David C. , Gori Ilaria , Haar Shlomi , Hoekstra Liesbeth , Jahanshad Neda , Jahanshad Neda , Jalbrzikowski Maria , Janssen Joost , King Joseph A. , Zaro Luisa L , Lerch Jason P. , Luna Beatriz , Martinho Mauricio M. , McGrath Jane , Medland Sarah E. , Muratori Filippo , Murphy Clodagh M. , Murphy Declan G.M. , O’Hearn Kirsten , Oranje Bob , Parellada Mara , Puig Olga , Retico Alessandra , Rosa Pedro , Rubia Katya , Shook Devon , Taylor Margot , Tosetti Michela , Wallace Gregory L. , Zhou Fengfeng , Thompson Paul , Fisher Simon E. , Buitelaar Jan K. , Francks Clyde 
Published: March 2019

AbstractBackgroundLeft-right asymmetry is an important organizing feature of the healthy brain. Various studies have reported altered structural brain asymmetry in autism spectrum disorder (ASD). However, findings have been inconsistent, likely due to limited sample sizes and low statistical power.MethodsWe investigated 1,774 subjects with ASD and 1,809 controls, from 54 datasets, for differences in the asymmetry of thickness and surface area of 34 cerebral cortical regions. We also examined global hemispheric measures of cortical thickness and area asymmetry, and volumetric asymmetries of subcortical structures. Data were obtained via the ASD Working Group of the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium. T1-weighted MRI data were processed with a single protocol using FreeSurfer and the Desikan-Killiany atlas.ResultsASD was significantly associated with reduced leftward asymmetry of total hemispheric average cortical thickness, compared to controls. Eight regional thickness asymmetries, distributed over the cortex, also showed significant associations with diagnosis after correction for multiple comparisons, for which asymmetry was again generally lower in ASD versus controls. In addition, the medial orbitofrontal surface area was less rightward asymmetric in ASD than controls, and the putamen volume was more leftward asymmetric in ASD than controls. The largest effect size had Cohen’sd= 0.15. Most effects did not depend on age, sex, IQ, or disorder severity.ConclusionAltered lateralized neurodevelopment is suggested in ASD, affecting widespread cortical regions with diverse functions. Large-scale analysis was necessary to reliably detect, and accurately describe, subtle alterations of structural brain asymmetry in this disorder.
Comparison Between Normobaric Hypoxia Altitude Simulation Test and Altitude Hypoxia Predictive Equations in Cystic Fibrosis Patients
Authors: Costa Christine , Barros André , Rodrigues João Valença , Staats Richard , Alves Mariana , Cardim Pilar , Lopes Carlos , Barbara Cristina , Moita Luís F. , Moreira Susana 
Published: March 2019

AbstractBackground:The Hypoxia Altitude Simulation Test (HAST) is the Gold Standard to evaluate hypoxia in response to altitude and to decide on in-flight requirements for oxygen supplementation. Several equations are available to predict PaO2 in altitude (PaO2alt), but it remains unclear whether their predictive value is equivalent. We aimed to compare the results obtained by the available methods in a population of cystic fibrosis (CF) adults.Methods:Eighty-eight adults (58 healthy controls and 30 CF patients) performed a spirometry followed by an HAST. HAST results were compared with the predicted PaO2alt made by five equations: 1st: PaO2alt= 0,410 x PaO2ground + 1,7652; 2nd: PaO2alt= 0,519 x PaO2ground + 11,855 x FEV1 (L) − 1,760; 3rd: PaO2alt= 0,453 x PaO2ground + 0,386 x FEV1 (%) + 2,44; 4th: PaO2alt= 0,88 + 0,68 x PaO2ground; 5th: PaO2alt= PaO2ground − 26,6.Results:None of the controls required in-flight oxygen neither by HAST or by the five predictive equations. Eleven CF-patients had PaO2alt < 50 mmHg, accessed by HAST. The positive predictive value was 50% (1st), 87.5% (2nd and 3rd), 77.78% (4th) and 58.33% (5th). Areas under the curve were 78.95% (1st), 84.69% (2nd), 88.04% (3rd) and 78.95% (4th and 5th). FEV1 and PaO2ground were correlated with HAST results.Conclusions:The 3rd equation gave the best predictions in comparison with results obtained by HAST. However, because the individual differences found were substantial for all equations, we still recommend performing a HAST whenever possible to confidently access in-flight hypoxia and the need for oxygen.
Modulation of Rapid Visual Responses during Reaching by Multimodal Stimuli
Authors: Glover Isabel S , Baker Stuart N 
Published: March 2019

AbstractThe reticulospinal tract plays an important role in primate upper limb function, but methods for assessing its activity are limited. One promising approach is to measure rapid visual responses (RVRs) in arm muscle activity during a visually-cued reaching task; these may arise from a tecto-reticulospinal pathway. We investigated whether changes in reticulospinal excitability can be assessed non-invasively using RVRs, by pairing the visual stimuli of the reaching task with electrical stimulation of the median nerve, galvanic vestibular stimulation or loud sounds, all of which are known to activate the reticular formation.Surface electromyogram recordings were made from the right deltoid of healthy human subjects as they performed fast reaching movements towards visual targets. Stimuli were delivered up to 200ms before target appearance and RVR was quantified as the EMG amplitude in a window 75-125ms after visual target onset. Median nerve, vestibular and auditory stimuli all consistently facilitated the RVRs, as well as reducing the latency of responses. We propose that this reflects modulation of tecto-reticulospinal excitability, suggesting that the amplitude of RVRs can be used to assess changes in brainstem excitability non-invasively in humans.New & NoteworthyShort latency responses in arm muscles evoked during a visually-driven reaching task have previously been proposed to be tecto-reticulospinal in origin. We demonstrate that these responses can be facilitated by pairing the appearance of a visual target with stimuli that activate the reticular formation – median nerve, vestibular and auditory stimuli. We propose that this reflects non-invasive measurement and modulation of reticulospinal excitability.
Notch signaling restricts FGF pathway activation in parapineal cells to promote their collective migration
Authors: Wei Lu , Blader Patrick , Roussigné Myriam 
Published: March 2019

AbstractCoordinated migration of cell collectives is important during embryonic development and relies on cells integrating multiple mechanical and chemical cues. Recently, we described that focal activation of the FGF pathway promotes the migration of the parapineal in the zebrafish epithalamus. How FGF activity is restricted to leading cells in this system is, however, unclear. Here, we address the role of Notch signaling in modulating FGF activity within the parapineal. While Notch loss-of-function results in an increased number of parapineal cells activating the FGF pathway, global activation of Notch signaling decreases it; both contexts result in defects in parapineal migration and specification. Decreasing or increasing FGF signaling in a Notch loss-of-function context respectively rescues or aggravates parapineal migration defects without affecting parapineal cells specification. We propose that Notch signaling controls the migration of the parapineal through its capacity to restrict FGF pathway activation to a few leading cells.