bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pure Glaucoma Drugs Are Toxic to Immortalized Human Corneal Epithelial Cells, but They Do Not Destabilize Lipid Membranes
Authors: Robciuc Alexandra , Witos Joanna , Ruokonen Suvi-Katriina , Rantamäki Antti H. , Pisella Pierre-Jean , Wiedmer Susanne K. , Holopainen Juha M. 
Published: August 2017

Purpose:
Most pure glaucoma drugs (pGDs) are hydrophobic substances intended to reduce elevated intraocular pressure. The aims of our study were to determine the toxicity of pGDs (brimonidine tartrate, brinzolamide, latanoprost, timolol maleate, and pilocarpine hydrochloride) on ocular surface cells and to establish whether their toxicity is subsequent to cellular membrane destabilization.

Methods:
The toxicity of clinically efficient doses of pGDs was measured at different time points in a cell culture of human corneal epithelial cells using a redox indicator. pGD interaction with the plasma membrane was analyzed using a hemolysis assay and liposome electrokinetic chromatography. The capacity of pGDs to induce endoplasmic reticulum stress was investigated by immunoblotting.

Results:
The toxicity assay showed that all pGDs decrease the viability of the epithelial cells to variable degrees. Early toxicity was measured for 4% pilocarpine and 0.15% brimonidine with 60% cell death at 4 hours, whereas 2% pilocarpine and 0.005% latanoprost showed almost 100% toxicity but only after 16 hours. The hemolysis assay and liposome electrokinetic chromatography experiments suggested that interaction between pGDs and lipid membranes is weak and cannot explain cell death through lysis. Immunoblotting revealed that the drugs activate endoplasmic reticulum stress and, with the exception of pilocarpine, have the capacity to induce apoptosis through upregulation of C/EBP homologous protein.

Conclusions:
Our study indicates that all studied pGDs decrease the viability of the corneal epithelial cells, but none of the tested compounds were able to destabilize cellular membranes. The pGDs seem to be internalized and can induce apoptosis through C/EBP homologous protein recruitment.
Cerebrospinal Fluid Cathelicidin Correlates With the Bacterial Load and Outcomes in Childhood Bacterial Meningitis
Authors: Savonius Okko , Helve Otto , Roine Irmeli , Andersson Sture , Saukkoriipi Annika , González Mata Antonio , Peltola Heikki , Pelkonen Tuula 
Published: August 2017

Background:
Large cerebrospinal fluid (CSF) bacterial load in bacterial meningitis (BM) relates to poor outcome. However, the antimicrobial peptide cathelicidin seems important to host defense. We studied how cathelicidin concentrations and bacterial load in CSF relate in childhood BM and to what extent they may predict the disease outcome.

Methods:
The patient data originated from a large prospective clinical trial in Latin America in 1996–2003 in which the CSF samples were collected on admission (CSF1) and 12–24 hours later (CSF2). The cathelicidin concentrations were measured by enzyme-linked immunosorbent assay and the CSF bacterial load by real-time polymerase chain reaction. This analysis comprised 76 children with meningitis caused by Haemophilus influenzae type b (n = 44), Streptococcus pneumoniae (n = 28) or Neisseria meningitidis (n = 4).

Results:
The cathelicidin concentration correlated with the bacterial genome count in both samples (CSF1: ρ = 0.531, P < 0.001; CSF2: ρ = 0.553, P < 0.001). A high CSF1 ratio of cathelicidin to the bacterial genome count was associated with fewer audiologic sequelae (odds ratio: 0.11, 95% confidence interval: 0.02–0.61, P = 0.01) and more favorable neurologic outcomes (odds ratio: 3.95, 95% confidence interval: 1.22–12.8, P = 0.02), but not with better survival.

Conclusions:
In conclusion, CSF cathelicidin and the bacterial load were closely related in childhood BM. A high initial cathelicidin-to-bacterial genome count ratio predicted better outcomes in survivors.
No Effects of D-Cycloserine Enhancement in Exposure With Response Prevention Therapy in Panic Disorder With Agoraphobia
Authors: Hofmeijer-Sevink Mieke Klein , Duits Puck , Rijkeboer Marleen M. , Hoogendoorn Adriaan W. , van Megen Harold J. , Vulink Nienke C. , Denys Damiaan A. , van den Hout Marcel A. , van Balkom Anton J. , Cath Danielle C. 
Published: August 2017

Abstract

Purpose/Background
D-cycloserine (DCS) is a partial N-methyl-D-aspartate receptor agonist that potentially augments response to exposure therapy in anxiety disorders by enhancing extinction learning. This randomized, double-blinded, placebo-controlled augmentation trial examined (1) the effectiveness of adding 125 mg of DCS to exposure therapy (before or directly after the first 6 treatment sessions) in patients with panic disorder with agoraphobia and (2) the effectiveness of DCS augmentation preceding exposure relative to DCS augmentation directly postexposure.

Methods/Procedures
Fifty-seven patients were allocated to 1 of 3 medication conditions (placebo and pre-exposure and postexposure DCS) as an addition to 6 exposure sessions within a 12-session exposure and response prevention protocol. The primary outcome measure was the mean score on the “alone” subscale of the Mobility Inventory (MI).

Findings/Results
No differences were found in treatment outcome between DCS and placebo, administered either pre-exposure or postexposure therapy, although at 3-month follow-up, the DCS postexposure group compared with DCS pre-exposure, exhibited greater symptom reduction on the MI-alone subscale. Ancillary analyses in specific subgroups (responders vs nonresponders, early vs late responders, severely vs mildly affected patients) did not reveal any between-group DCS versus placebo differences. Finally, the study did not find an effect of DCS relative to placebo to be specific for successful exposure sessions.

Implications/Conclusions
This study does not find an effect of augmentation with DCS in patients with severe panic disorder and agoraphobia administered either pretreatment or directly posttreatment sessions. Moreover, no preferential effects are revealed in specific subgroups nor in successful exposure sessions. Yet, a small effect of DCS administration postexposure therapy cannot be ruled out, given the relatively small sample size of this study.
The Experience of Litigation From the Perspective of Midwives in Iran
Authors: Peyman Akram , Nayeri Nahid Dehghan , Bandboni Mohammad Esmaeilpour , Moghadam Zahra Behboodi 
Published: August 2017

Introduction
Errors and notices to appear in court are a reality of life for many midwives and exert significant effects on both their professional and personal lives. Given the increasing population policies in place, this study was conducted to examine midwives' experiences of litigation in Iran.

Methods
A qualitative study was conducted in 2014 using an interpretive phenomenological approach. The interviews were recorded and transcribed and were then analyzed using the Diekelmann method.

Findings
Midwives who participated had professional experience ranging from 3 to 22 years at the time of the complaints. Five participants had received more than one complaint, and 10 participants were judged as guilty creating/leaving significant effects on various dimensions of their lives.

Conclusion
The present research disclosed four main themes from the interviews including feeling ruined by the complaints, being conflicted between denial and belief, having shattered hopes of release, and experiencing the slowed-down rhythm of midwifery. From these, a basic pattern of “living in despair” was extracted. Litigation is a painful experience for midwives. Anxiety regarding compensation for the patients' losses, public judgment, prolonged litigations, and undermined professional dignity create physical and psychological ramifications for these midwives. Negative feelings about litigation, compounded by the lack of legal support from the authorities, cause a sense of hopelessness regarding the future of the midwifery profession.
Injury of the Hypothalamus in Patients With Hypoxic–Ischemic Brain Injury
Authors: Jang Sung Ho , Kwon Hyeok Gyu 
Published: August 2017

Objectives
The survival rate for hypoxic–ischemic brain injury (HI-BI) is less than 20%. Several brain regions, including the caudate, hippocampus, and hypothalamus, are vulnerable to HI-BI. Hypothalamus is involved in regulation of temperature, sleep-wakefulness cycle, emotional behavior, and memory function. Using diffusion tensor imaging, we examined injury of the hypothalamus in patients with HI-BI.

Methods
Twelve patients with HI-BI and 27 healthy control subjects were recruited. The region of interest was defined for the hypothalamus and the fractional anisotropy and apparent diffusion coefficient were measured.

Results
The fractional anisotropy value was significantly lower in the patient group compared with the control group (P < 0.05), whereas the apparent diffusion coefficient value was significantly higher compared with that of the control group (P < 0.05). In the individual analysis, 7 (58.3%) of 12 patients and 14 (58.3%) of 24 hemispheres showed a decrement or increment of more than two SDs in either fractional anisotropy or apparent diffusion coefficient values compared with the control group.

Conclusions
Using diffusion tensor imaging, injury of the hypothalamus was demonstrated in patients with HI-BI. Our methodology and results of this study would be helpful in research on the hypothalamus in patients with HI-BI.
Modeling of dynamic cerebrovascular reactivity to spontaneous and externally induced CO2 fluctuations in the human brain using BOLD-fMRI
Authors: Prokopiou Prokopis C. , Pattinson Kyle T. S. , Wise Richard G. , Mitsis Georgios D. 
Published: August 2017

AbstractIn this work, we investigate the regional characteristics of the dynamic interactions between arterial CO2 and BOLD (dynamic cerebrovascular reactivity - dCVR) during normal breathing and hypercapnic, externally induced step CO2 challenges. To obtain CVR curves at each voxel, we use a custom set of basis functions based on the Laguerre and gamma basis sets. This allows us to obtain robust dCVR estimates both in larger regions of interest (ROIs) as well as in individual voxels. We also implement classification schemes to identify brain regions with similar dCVR characteristics. Our results reveal considerable variability of dCVR across different brain regions, as well as during different experimental conditions (normal breathing and hypercapnia), suggesting a differential response of cerebral vasculature to spontaneous CO2 fluctuations and larger, externally induced CO2 changes. The clustering results suggest that anatomically distinct brain regions exhibit different dCVR curves that do not exhibit the standard, positive valued curves that have been previously reported using measurements of global cerebral blood flow or using larger ROIs. They also revealed a consistent set of dCVR cluster shapes for resting and forcing conditions that exhibited different distribution patterns across brain voxels.
On the Stability Landscape of the Human Gut Microbiome: Implications for Microbiome-based Therapies
Authors: Gibson Travis E. , Carey Vincent , Bashan Amir , Hohmann Elizabeth L. , Weiss Scott T. , Liu Yang-Yu 
Published: August 2017

AbstractUnderstanding how gut microbial species determine their abundances is crucial in developing any microbiome-based therapy. Towards that end, we show that the compositions of our gut microbiota have characteristic and attractive steady states, and hence respond to perturbations in predictable ways. This is achieved by developing a new method to analyze the stability landscape of the human gut microbiome. In order to illustrate the efficacy of our method and its ecological interpretation in terms of asymptotic stability, this novel method is applied to various human cohorts, including large cross-sectional studies, long longitudinal studies with frequent sampling, and perturbation studies via fecal microbiota transplantation, antibiotic and probiotic treatments. These findings will facilitate future ecological modeling efforts in human microbiome research. Moreover, the method allows for the prediction of the compositional shift of the gut microbiome during the fecal microbiota transplantation process. This result holds promise for translational applications, such as, personalized donor selection when performing fecal microbiota transplantations.One Sentence SummaryA new method for analyzing the stability landscape of the human gut microbiome and predicting its steady-state composition is developed.
Desiccation plasticity and diapause in the Argentinian pearlfishAustrolebias bellottii
Authors: Van Dooren Tom J M , Varela-Lasheras Irma 
Published: August 2017

AbstractBackgroundThe annual life history strategy with diapauses evolved repeatedly in killifish. To understand their and to characterize their variation between species, patterns of desiccation plasticity seem central. Plasticity might have played a role in the origin of these developmental arrests, when annual fish evolved from non-annual ones. The consequences of desiccation on survival and developmental rates of embryos of annual fish are poorly known. Using detailed demographic modelling of embryonal life histories, we investigate plasticity for desiccation in the Argentinian pearlfishAustrolebias bellottii. The treatment protocol contains changing environmental conditions with successive phases of mild desiccation and rewetting.ResultsWe observed no clear diapause II and thus no increased incidence caused by mild and prolonged desiccation. Embryos arrest development in the pre-hatching stage (DIII) or in the dispersed cell phase (DI) irrespective of environmental conditions. There are limited effects of desiccation on survival, limited developmental delays and an acceleration of development into the pre-hatching stage. We found significant parental variance components on developmental rates, but hardly any effect of parental age. Hatching probabilities increased with age, when embryos had been in air at 100% RH and increased further when embryos were rewetted a second time after a two month interval.ConclusionsMild desiccation and rewetting affect survival, rates of development and hatching probability, but not the fractions of embryos that arrest development in particular stages. We can conclude that the incidences of diapause have become relatively independent of the occurrence of mild desiccation, as if they have become assimilated. In contrast to the responses to mild desiccation observed in the non-annual rivulids,Austrolebiasaccelerates development into the pre-hatching stage.
When conflict cannot be avoided: executive control dominates early selective sensory modulations during cognitive conflict
Authors: Itthipuripat Sirawaj , Deering Sean , Serences John T. 
Published: August 2017

AbstractWhen different sources of sensory information suggest competing behavioral responses, the efficiency of decision-making is impaired. Prior work suggests that at least two mechanisms may play a role in mitigating this interference: using early selective attention to extract the most relevant sensory inputs to avoid conflict or increasing the efficiency of the executive control network to resolve conflict during post-perceptual processing. To test these alternatives, we combined a stimulus-frequency tagging technique with a classic color-word Stroop paradigm, where color-bar targets and letter-string distractors were simultaneously flickered at different frequencies. Using electroencephalography (EEG), we measured the quality of early sensory processing by assessing the amplitude of steady-state visually evoked potentials (SSVEPs) elicited by the targets and distractors. We also measured the engagement of the executive control network by assessing changes in frontal theta (4-7Hz) and posterior alpha oscillations (8-14Hz). Counter to the ‘early selective sensory modulation’ account, the amplitude of the SSVEP response was not modulated by manipulations of color/word congruency, while the frontal theta activity increased and the posterior alpha activity decreased in response to conflict. Moreover, target-related SSVEP amplitude was not correlated with response times (RTs) and a higher (not lower) distractor-related SSVEP amplitude predicted faster RTs. On the other hand, the amplitude of the frontal theta and alpha activity was highly correlated with RTs, irrespective of conflict levels. Over all, these results highlight the dominant role of the executive control network in conflict resolution during post-perceptual processing.Significance StatementConflicting information interferes with decision-making. However, this interference can be mitigated either by extracting the most relevant inputs during early sensory processing or by increasing the efficiency of the executive control processes to resolve conflict. By measuring electroencephalography (EEG) in humans performing a modified color-word Stroop task, we examined early sensory responses evoked by targets and distractors while simultaneously monitoring frontal theta and posterior alpha oscillations to index the activation of the executive control network. We found evidence that the executive control network played a more prominent role in resolving conflict.
CDX4 regulates the progression of neural maturation in the spinal cord
Authors: Joshi Piyush , Darr Andrew J. , Skromne Isaac 
Published: August 2017

ABSTRACTThe progressive maturation of cells down differentiation lineages is controlled by collaborative interactions between networks of extracellular signals and intracellular transcription factors. In the vertebrate spinal cord, FGF, Wnt and Retinoic Acid signaling pathways regulate the progressive caudal-to-rostral maturation of neural progenitors by regulating a poorly understood gene regulatory network of transcription factors. We have mapped out this gene regulatory network in the chicken pre-neural tube, identifying CDX4 as a dual-function core component that simultaneously regulates gradual loss of cell potency and acquisition of differentiation states: in a caudal-to-rostral direction, CDX4 represses the early neural differentiation markerNkx1.2and promotes the late neural differentiation markerPax6.Significantly, CDX4 prevents premature PAX6-dependent neural differentiation by blockingNgn2activation. This regulation of CDX4 overPax6is restricted to the rostral pre-neural tube by Retinoic Acid signaling. Together, our results show that in the spinal cord, CDX4 is part of the gene regulatory network controlling the sequential and progressive transition of states from high to low potency during neural progenitor maturation. Given CDX well-known involvement inHoxgene regulation, we propose that CDX factors coordinate the maturation and axial specification of neural progenitor cells during spinal cord development.
Daytime eyeshine contributes to pupil camouflage in a cryptobenthic marine fish
Authors: Santon Matteo , Bitton Pierre-Paul , Harant Ulrike K. , Michiels Nico K. 
Published: August 2017

ABSTRACTOcular reflectors enhance eye sensitivity in dim light, but can produce reflected eyeshine when illuminated. Most teleost fish occlude their reflectors during the day. The opposite is observed in cryptic sit-and-wait predators such as scorpionfish and toadfish, where reflectors are occluded at night and exposed during the day. This results in daytime eyeshine, proposed to enhance pupil camouflage by reducing the contrast between the otherwise black pupil and the surrounding tissue. In this study, we test this hypothesis in the scorpionfishScorpaena porcusand show that eyeshine is the result of two mechanisms: the previously describedStratum Argenteum Reflected(SAR) eyeshine, andPigment Epithelium Transmitted(PET) eyeshine, a newly described mechanism for this species. We confirm that the ocular reflector is exposed only when the eye is light-adapted, and present field measurements to show that eyeshine reduces pupil contrast against the iris. We then estimate the relative contribution of SAR and PET eyeshine to pupil brightness. Visual models for different light scenarios in the field show that daytime eyeshine enhances pupil camouflage from the perspective of a prey fish. We propose that the reversed occlusion mechanism of some cryptobenthic predators has evolved as a compromise between camouflage and vision.
Cortico-Cerebellar Networks Drive Sensorimotor Learning in Speech
Authors: Lametti Daniel R. , Smith Harriet J. , Freidin Phoebe , Watkins Kate E. 
Published: August 2017

AbstractThe motor cortex and cerebellum are thought to be critical for learning and maintaining motor behaviours. Here we use tDCS to test the role of the motor cortex and cerebellum in sensorimotor learning in speech. During productions of ‘head’, ‘bed’, and ‘dead’, the first formant of the vowel sound was altered in real-time towards the first formant of the vowel sound in ‘had’, ‘bad’, and ‘dad’. Compensatory changes in first and second formant production were used as a measure of motor adaptation. TDCS to either the motor cortex or the cerebellum improved sensorimotor learning in speech compared to sham stimulation. However, in the case of cerebellar tDCS, production changes were restricted to the source of the acoustical error (i.e. the first formant). Motor cortex tDCS drove production changes that offset errors in the first formant, but, unlike cerebellar tDCS, adaptive changes in the second formant also occurred. The results suggest that motor cortex and cerebellar tDCS have both shared and dissociable effects on motor adaptation. The study provides initial causal evidence in speech production that the motor cortex and the cerebellum support different aspects of sensorimotor learning. We propose that motor cortex tDCS drives sensorimotor learning towards previously learned patterns of movement, while cerebellar tDCS focuses sensorimotor learning on error correction.
Decoupling the roles of cell shape and mechanical stress in orienting and cueing epithelia mitosis
Authors: Nestor-Bergmann Alexander , Stooke-Vaughan Georgina A. , Goddard Georgina K. , Starborg Tobias , Jensen Oliver E. , Woolner Sarah 
Published: August 2017

AbstractDistinct mechanisms involving cell shape and mechanical force are known to influence the rate and orientation of division in cultured cells. However, uncoupling the impact of shape and force in tissues remains challenging. Combining stretching ofXenopus laevistissue with a novel method of inferring relative mechanical stress, we find separate roles for cell shape in orientating division and mechanical stress in cueing division. We demonstrate that division orientation is best predicted by an axis of cell shape defined by the position of tricellular junctions (TCJs), which aligns exactly with the principal axis of local cell stress rather than the tissue-level stress. The alignment of division to cell shape requires functional cadherin and the localisation of the spindle orientation protein, LGN, to TCJs, but is not sensitive to relative cell stress magnitude. In contrast, cell proliferation rate is more directly regulated by mechanical stress, being correlated with relative isotropic stress, and can be decoupled from cell shape when myosin II is depleted.