bluuebunny/crossref_metadata_2025_split huggingface dataset:
Migraine and the risk of cardiovascular and cerebrovascular events: a meta-analysis of 16 cohort studies including 1 152 407 subjects
Authors: Mahmoud Ahmed N , Mentias Amgad , Elgendy Akram Y , Qazi Abdul , Barakat Amr F , Saad Marwan , Mohsen Ala , Abuzaid Ahmed , Mansoor Hend , Mojadidi Mohammad K , Elgendy Islam Y 
Published: March 2018

ObjectivesTo perform an updated meta-analysis to evaluate the long-term cardiovascular and cerebrovascular outcomes among migraineurs.SettingA meta-analysis of cohort studies performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Data sourcesThe MEDLINE, Web of Science and Cochrane Central Register of Controlled Trials databases were searched for relevant articles.ParticipantsA total of 16 cohort studies (18 study records) with 394 942 migraineurs and 757 465 non-migraineurs were analysed.Primary and secondary outcome measuresMajor adverse cardiovascular and cerebrovascular events (MACCE), stroke (ie, ischaemic, haemorrhagic or non-specified), myocardial infarction (MI) and all-cause mortality. The outcomes were reported at the longest available follow-up.Data analysisSummary-adjusted hazard ratios (HR) were calculated by random-effects Der-Simonian and Liard model. The risk of bias was assessed by the Newcastle-Ottawa Scale.ResultsMigraine was associated with a higher risk of MACCE (adjusted HR 1.42, 95% confidence interval [CI] 1.26 to 1.60, P<0.001, I2=40%) driven by a higher risk of stroke (adjusted HR 1.41, 95% CI 1.25 to 1.61, P<0.001, I2=72%) and MI (adjusted HR 1.23, 95% CI 1.03 to 1.43, P=0.006, I2=59%). There was no difference in the risk of all-cause mortality (adjusted HR 0.93, 95% CI 0.78 to 1.10, P=0.38, I2=91%), with a considerable degree of statistical heterogeneity between the studies. The presence of aura was an effect modifier for stroke (adjusted HR aura 1.56, 95% CI 1.30 to 1.87 vs adjusted HR no aura 1.11, 95% CI 0.94 to 1.31, Pinteraction=0.01) and all-cause mortality (adjusted HR aura 1.20, 95% CI 1.12 to 1.30 vs adjusted HR no aura 0.96, 95% CI 0.86 to 1.07, Pinteraction<0.001).ConclusionMigraine headache was associated with an increased long-term risk of cardiovascular and cerebrovascular events. This effect was due to an increased risk of stroke (both ischaemic and haemorrhagic) and MI. There was a moderate to severe degree of heterogeneity for the outcomes, which was partly explained by the presence of aura.PROSPERO registration numberCRD42016052460.
Impacts of smoke-free public places legislation on inequalities in youth smoking uptake: study protocol for a secondary analysis of UK survey data
Authors: Anyanwu Philip Emeka , Craig Peter , Katikireddi Srinivasa Vittal , Green Michael James 
Published: March 2018

IntroductionSmoke-free public places legislation has been introduced in many countries to protect the public from the harmful effects of secondhand smoking. While evaluations of smoke-free policies have demonstrated major public health benefits, the impact on youth smoking and inequalities in smoking remains unclear. This project aims to evaluate how smoke-free public places legislation in the UK has impacted on inequalities in youth smoking uptake, and how much of any impact is via changes in parental smoking behaviour.Methods and analysisThe study will constitute secondary analyses of UK data (from the British Household Panel Survey and the Understanding Society study). Merging these datasets gives coverage of the period from 1994 to 2016. Missing data will be handled using multiple imputation. The primary outcomes are the rates and inequalities in initiation, experimentation, escalation to daily smoking and quitting among youths aged 11–15 years. Secondary outcomes include the prevalence of smoking among parents of these youths. Discrete-time event history analysis will be conducted to examine whether changes in the probability of youth smoking transitions are associated with the implementation of the smoke-free public places legislation; and whether any observed effects differ by socioeconomic position and parental smoking. A multilevel logistic regression model will be used to investigate whether there is a step change or change in trend for the prevalence of parental smoking after the policy was implemented. The models will be adjusted for relevant factors (including cigarette taxation, the change in the legal age for purchase of cigarettes and e-cigarette prevalence) that may be associated with the implementation of the legislation.Ethics and disseminationThis project will use anonymised survey data which have been collected following independent ethical review. The dissemination of the study findings will adopt multiple communication channels targeting both scientific and non-scientific audiences.
Neurophysiological changes in the visuomotor network after practicing a motor task
Authors: Gehringer James E. , Arpin David J. , Heinrichs-Graham Elizabeth , Wilson Tony W. , Kurz Max J. 
Published: March 2018

Although it is well appreciated that practicing a motor task updates the associated internal model, it is still unknown how the cortical oscillations linked with the motor action change with practice. The present study investigates the short-term changes (e.g., fast motor learning) in the α- and β-event-related desynchronizations (ERD) associated with the production of a motor action. To this end, we used magnetoencephalography to identify changes in the α- and β-ERD in healthy adults after participants practiced a novel isometric ankle plantarflexion target-matching task. After practicing, the participants matched the targets faster and had improved accuracy, faster force production, and a reduced amount of variability in the force output when trying to match the target. Parallel with the behavioral results, the strength of the β-ERD across the motor-planning and execution stages was reduced after practice in the sensorimotor and occipital cortexes. No pre/postpractice changes were found in the α-ERD during motor planning or execution. Together, these outcomes suggest that fast motor learning is associated with a decrease in β-ERD power. The decreased strength likely reflects a more refined motor plan, a reduction in neural resources needed to perform the task, and/or an enhancement of the processes that are involved in the visuomotor transformations that occur before the onset of the motor action. These results may augment the development of neurologically based practice strategies and/or lead to new practice strategies that increase motor learning. NEW & NOTEWORTHY We aimed to determine the effects of practice on the movement-related cortical oscillatory activity. Following practice, we found that the performance of the ankle plantarflexion target-matching task improved and the power of the β-oscillations decreased in the sensorimotor and occipital cortexes. These novel findings capture the β-oscillatory activity changes in the sensorimotor and occipital cortexes that are coupled with behavioral changes to demonstrate the effects of motor learning.
Visuomotor learning is dependent on direction-specific error saliency
Authors: Jiang Wanying , Yuan Xianzhi , Yin Cong , Wei Kunlin 
Published: March 2018

People perceive better in cardinal directions compared with oblique ones. This directional effect, called oblique effect, has been documented in perception studies for a long time. However, typical motor studies do not differentiate learning in different directions. In this study we identify a significant directional effect in motor learning using visuomotor rotation paradigms. We find that adaptation to visual perturbations yields more savings when both initial learning and relearning are performed in cardinal directions than in oblique directions. We hypothesize that this directional effect arises from relatively higher error saliency in cardinal directions. Consistent with this hypothesis, we successfully increased savings in the oblique directions, which showed no saving effect before, by enhancing the error saliency with augmented visual feedback during learning. Our findings suggest that movement direction plays an important role in motor learning, especially when learning signals are direction specific. Our results also provide new insights about the role of motor errors in the formation and retrieval of motor memory and practical implications for promoting learning in motor rehabilitation and athletic training. NEW & NOTEWORTHY People perceive better when the stimulus is in cardinal directions than in oblique directions. Whether a similar directional effect exists in motor learning is unknown. Using a motor learning paradigm, we show that people relearn to compensate for a previously encountered perturbation faster when they move in cardinal directions than when they move in oblique directions. Further experimentation supports that this motor directional effect likely results from better sensory saliency of motor errors in cardinal directions.
Proximal and distal modulation of neural activity by spatially confined optogenetic activation with an integrated high-density optoelectrode
Authors: Libbrecht Sarah , Hoffman Luis , Welkenhuysen Marleen , Van den Haute Chris , Baekelandt Veerle , Braeken Dries , Haesler Sebastian 
Published: March 2018

Optogenetic manipulations are widely used for investigating the contribution of genetically identified cell types to behavior. Simultaneous electrophysiological recordings are less common, although they are critical for characterizing the specific impact of optogenetic manipulations on neural circuits in vivo. This is at least in part because combining photostimulation with large-scale electrophysiological recordings remains technically challenging, which also poses a limitation for performing extracellular identification experiments. Currently available interfaces that guide light of the appropriate wavelength into the brain combined with an electrophysiological modality suffer from various drawbacks such as a bulky size, low spatial resolution, heat dissipation, or photovoltaic artifacts. To address these challenges, we have designed and fabricated an integrated ultrathin neural interface with 12 optical outputs and 24 electrodes. We used the device to measure the effect of localized stimulation in the anterior olfactory cortex, a paleocortical structure involved in olfactory processing. Our experiments in adult mice demonstrate that because of its small dimensions, our novel tool causes far less tissue damage than commercially available devices. Moreover, optical stimulation and recording can be performed simultaneously, with no measurable electrical artifact during optical stimulation. Importantly, optical stimulation can be confined to small volumes with approximately single-cortical layer thickness. Finally, we find that even highly localized optical stimulation causes inhibition at more distant sites. NEW & NOTEWORTHY In this study, we establish a novel tool for simultaneous extracellular recording and optogenetic photostimulation. Because the device is built using established microchip technology, it can be fabricated with high reproducibility and reliability. We further show that even very localized stimulation affects neural firing far beyond the stimulation site. This demonstrates the difficulty in predicting circuit-level effects of optogenetic manipulations and highlights the importance of closely monitoring neural activity in optogenetic experiments.
Gap encoding by parvalbumin-expressing interneurons in auditory cortex
Authors: Keller Clifford H. , Kaylegian Katherine , Wehr Michael 
Published: March 2018

Synaptic inhibition shapes the temporal processing of sounds in auditory cortex, but the contribution of specific inhibitory cell types to temporal processing remains unclear. We recorded from parvalbumin-expressing (PV+) interneurons in auditory cortex to determine how they encode gaps in noise, a model of temporal processing more generally. We found that PV+ cells had stronger and more prevalent on-responses, off-responses, and postresponse suppression compared with presumed pyramidal cells. We summarize this pattern of differences as “deeper modulation” of gap responses in PV+ cells. Response latencies were also markedly faster for PV+ cells. We found a similar pattern of deeper modulation and faster latencies for responses to white noise bursts, suggesting that these are general properties of on- and off-responses in PV+ cells rather than specific features of gap encoding. These findings are consistent with a role for PV+ cells in providing dynamic gain control by pooling local activity. NEW & NOTEWORTHY We found that parvalbumin-expressing (PV+) interneurons in auditory cortex showed more deeply modulated responses to both gaps in noise and bursts of noise, suggesting that they are optimized for the rapid detection of stimulus transients.
Mechanistic Modeling of Antibody–Drug Conjugate Internalization at the Cellular Level Reveals Inefficient Processing Steps
Authors: Durbin Kenneth R. , Phipps Colin , Liao Xiaoli 
Published: March 2018

Abstract
Antibody–drug conjugates (ADC) offer an avenue for specific drug delivery to target cells. Here, parameters with important roles in the cellular processing of ADCs were quantitatively measured for Ab033, an antibody against EGFR. In EGFR-overexpressing cancer cell lines, Ab033 internalized at rates of 0.047/min and 0.15/min for A431 and H441 cells, respectively. Once internalized, Ab033 either trafficked to the lysosome or was recycled; up to 45% of internalized Ab033 returned to the cell surface. Despite such recycling, intracellular accumulation of Ab033 continually increased over 24 hours. Ab033 was conjugated to form a dual toxin ADC containing both cleavable and non-cleavable linker-drug payloads for release rate comparisons. Intracellular concentrations of freed drug from cleavable linker were greater than from non-cleavable linker and exceeded 5 × 106 drug molecules per A431 cell after 24 hours. Compared with intracellular antibody accumulation, formation of released drug was delayed, likely due to the time needed for endo-lysosomal trafficking and subsequent linker/antibody proteolysis. Informed by the quantitative data, a cellular ADC model was constructed and used to summarize processing inefficiencies. Modeling simulations were conducted to determine parameter sensitivity on intracellular drug concentrations, with rates of EGFR internalization and recycling as well as ADC trafficking found to be the most sensitive toward final intracellular drug concentrations. Overall, this study shows Ab033 ADCs to be a viable strategy for delivery of cytotoxic drugs into tumor cells with subsequent modeling efforts able to highlight key processing steps to be improved for increased drug delivery. Mol Cancer Ther; 17(6); 1341–51. ©2018 AACR.
Itraconazole-Induced Inhibition on Human Esophageal Cancer Cell Growth Requires AMPK Activation
Authors: Chen Min-Bin , Liu Yuan-Yuan , Xing Zhao-Yu , Zhang Zhi-Qing , Jiang Qin , Lu Pei-Hua , Cao Cong 
Published: March 2018

Abstract
We here evaluated the antiesophageal cancer cell activity by the antifungal drug itraconazole. Our results show that μg/mL concentrations of itraconazole potently inhibited survival and proliferation of established (TE-1 and Eca-109) and primary human esophageal cancer cells. Itraconazole activated AMPK signaling, which was required for subsequent esophageal cancer cell death. Pharmacologic AMPK inhibition, AMPKα1 shRNA, or dominant negative mutation (T172A) almost completely abolished itraconazole-induced cytotoxicity against esophageal cancer cells. Significantly, itraconazole induced AMPK-dependent autophagic cell death (but not apoptosis) in esophageal cancer cells. Furthermore, AMPK activation by itraconazole induced multiple receptor tyrosine kinases (RTKs: EGFR, PDGFRα, and PDGFRβ), lysosomal translocation, and degradation to inhibit downstream Akt activation. In vivo, itraconazole oral gavage potently inhibited Eca-109 tumor growth in SCID mice. It was yet ineffective against AMPKα1 shRNA-expressing Eca-109 tumors. The in vivo growth of the primary human esophageal cancer cells was also significantly inhibited by itraconazole administration. AMPK activation, RTK degradation, and Akt inhibition were observed in itraconazole-treated tumors. Together, itraconazole inhibits esophageal cancer cell growth via activating AMPK signaling. Mol Cancer Ther; 17(6); 1229–39. ©2018 AACR.
Synthetic Lethality of PARP Inhibition and Ionizing Radiation is p53-dependent
Authors: Sizemore Steven T. , Mohammad Rahman , Sizemore Gina M. , Nowsheen Somaira , Yu Hao , Ostrowski Michael C. , Chakravarti Arnab , Xia Fen 
Published: March 2018

Abstract
PARP inhibitors (PARPi) are potentially effective therapeutic agents capable of inducing synthetic lethality in tumors with deficiencies in homologous recombination (HR)-mediated DNA repair such as those carrying BRCA1 mutations. However, BRCA mutations are rare, the majority of tumors are proficient in HR repair, and thus most tumors are resistant to PARPi. Previously, we observed that ionizing radiation (IR) initiates cytoplasmic translocation of BRCA1 leading to suppression of HR-mediated DNA repair and induction of synthetic PARPi lethality in wild-type BRCA1 and HR-proficient tumor cells. The tumor suppressor p53 was identified as a key factor that regulates DNA damage–induced BRCA1 cytoplasmic sequestration following IR. However, the role of p53 in IR-induced PARPi sensitization remains unclear. This study elucidates the role of p53 in IR-induced PARPi cytotoxicity in HR-proficient cancer cells and suggests p53 status may help define a patient population that might benefit from this treatment strategy. Sensitization to PARPi following IR was determined in vitro and in vivo utilizing human breast and glioma tumor cells carrying wild-type BRCA1 and p53, and in associated cells in which p53 function was modified by knockdown or mutation. In breast and glioma cells with proficient HR repair, IR-induced BRCA1 cytoplasmic sequestration, HR repair inhibition, and subsequent PARPi sensitization in vitro and in vivo was dependent upon functional p53.
Implications: Implications: p53 status determines PARP inhibitor sensitization by ionizing radiation in multiple BRCA1 and HR-proficient tumor types and may predict which patients are most likely to benefit from combination therapy. Mol Cancer Res; 16(7); 1092–102. ©2018 AACR.
Langmuir Turbulence in Coastal Zones: Structure and Length Scales
Authors: Shrestha Kalyan , Anderson William , Kuehl Joseph 
Published: March 2018

AbstractLangmuir turbulence is a boundary layer oceanographic phenomenon of the upper layer that is relevant to mixing and vertical transport capacity. It is a manifestation of imposed aerodynamic stresses and the aggregate horizontal velocity profile due to orbital wave motion (the so-called Stokes profile), resulting in streamwise-elongated, counterrotating cells. The majority of previous research on Langmuir turbulence has focused on the open ocean. Here, we investigate the characteristics of coastal Langmuir turbulence by solving the grid-filtered Craik–Leibovich equations where the distinction between open and coastal conditions is a product of additional bottom boundary layer shear. Studies are elucidated by visualizing Langmuir cell vortices using isosurfaces of Q. We show that different environmental forcing conditions control the length scales of coastal Langmuir cells. We have identified regimes where increasing the Stokes drift velocity and decreasing surface wind stress both act to change the horizontal size of coastal Langmuir cells. Furthermore, wavenumber is also responsible in setting the horizontal extent Ls of Langmuir cells. Along with that, wavenumber that is linked to the Stokes depth δs controls the vertical extent of small-scale vortices embedded within the upwelling limb, while the downwelling limb occupies the depth of the water column H for any coastal surface wave forcing (i.e., and ). Additional simulations are included to demonstrate insensitivity to the grid resolution and aspect ratio.
Games Analysis Treatment of Social Isolation in a Gender Disturbed Boy
Authors: Marlowe Mike 
Published: March 2018

The effectiveness of a therapeutic motor development program in increasing motor development, sex-appropriate play patterns, and peer acceptance was investigated in a 10-year-old, gender-disturbed male child. The motor development program was based on the games analysis model. Pretest-posttest and follow-up assessments of the child's peer status and sex-typed games choices indicated he had made gains in peer acceptance and in sex-appropriate play. Movement profile sheets indicated the child had progressed in the motor behaviors of striking, catching, and kicking. The results of the study are discussed with regard to developing patterns of play based on individually based activities.
Where Are We in the Education of Emotionally Disturbed Children?
Authors: Zabel Robert H. , Paul James L. 
Published: March 2018

The major thesis of this paper is that some of the most dramatic gains in special education have been in the education of emotionally disturbed children. Unfortunately, the converse is equally true — some of the most pressing needs in special education are evident in this area. A minor, though significant, theme is that, while the field of emotional disturbance has perhaps the most shallow pedogogical roots of any category of exceptionality in special education, it has the deepest philosophical and psychological roots. This could be an asset in the present context of decline in support for professional schools of education. Other categorical areas of special education have had more primary affiliation with pedagogy, whereas the education of emotionally disturbed children has had more basic affiliation with psychology. I will first discuss the strengths of the area and selected accomplishments and changes during the past 20 years — the approximate total history — as a significant area of education. I will then focus on some of the challenges and opportunities for growth. My discussion of our strengths is divided into three parts: (a) maturing and change in our perspective, (b) areas in which we have been in the vanguard of special education, and (c) specific gains we have made.
Can functional task exercise improve executive function and contribute to functional balance in older adults with mild cognitive impairment? A pilot study
Authors: Law Lawla LF , Fong Kenneth NK , Yau Matthew MK 
Published: March 2018

Introduction Individuals with cognitive impairment are more susceptible to falls associated with decreased executive function and balance. This pilot study investigated whether functional task exercise could improve executive function, which might further affect the functional balance in older adults with mild cognitive impairment. Method This was a single-group pre-test/post-test pilot. A total of 43 participants completed a 10-week structured functional task exercise programme, performing simulated functional tasks. Paired-samples t-test was performed to evaluate intervention effects. Associations between variables were examined using Pearson's correlation coefficient. Multiple regression analysis was performed to explore the contribution of cognitive variables to functional balance. Results Significant improvements were shown in general cognitive functions, executive function, functional balance and functional status. All executive function outcomes were significantly associated with functional balance. Everyday problem-solving ability was the only significant cognitive contributor ( β = 0.407, p < 0.05) to functional balance after controlling for the confounding factors. Conclusion This pilot showed functional task exercise using simulated functional task as a means of intervention was feasible and was associated with observed improvements in executive function and functional balance in older adults with mild cognitive impairment, whereas everyday problem-solving ability was found to be associated with functional balance. Further well-designed controlled studies are needed to draw more definitive conclusions.