bluuebunny/crossref_metadata_2025_split huggingface dataset:
A hypoxia- and telomerase-responsive oncolytic adenovirus expressing secretable trimeric TRAIL triggers tumour-specific apoptosis and promotes viral dispersion in TRAIL-resistant glioblastoma
Authors: Oh Eonju , Hong JinWoo , Kwon Oh-Joon , Yun Chae-Ok 
Published: January 2018

AbstractGlioblastoma is a highly aggressive and malignant type of cancer that is apoptosis resistant and difficult to cure by conventional cancer therapies. In this regard, an oncolytic adenovirus that selectively targets the tumour tissue and induces tumour cell lysis is a promising treatment option. We designed and constructed a hypoxia-responsive and cancer-specific modified human telomerase reverse transcriptase (H5CmTERT) promoter to drive replication of an oncolytic adenovirus (H5CmTERT-Ad). To enhance the anti-tumour efficacy of H5CmTERT-Ad against malignant glioblastoma, we also generated an H5CmTERT-Ad expressing secretable trimeric tumour necrosis factor-related apoptosis-inducing ligand (H5CmTERT-Ad/TRAIL). H5CmTERT promoter-regulated oncolytic adenoviruses showed cancer-specific and superior cell-killing effect in contrast to a cognate control oncolytic adenovirus replicating under the control of the endogenous adenovirus promoter. The cancer cell-killing effects of H5CmTERT-Ad and H5CmTERT-Ad/TRAIL were markedly higher during hypoxia than normoxia owing to hypoxia responsiveness of the promoter. H5CmTERT-Ad/TRAIL showed more potent anti-tumour efficacy than H5CmTERT-Ad did in a xenograft model of TRAIL-resistant subcutaneous and orthotopic glioblastoma through superior induction of apoptosis and more extensive virus distribution in the tumour tissue. Altogether, our findings show that H5CmTERT-Ad/TRAIL can promote dispersion of an oncolytic adenovirus through robust induction of apoptosis in a highly TRAIL-resistant glioblastoma.
Group-I PAKs-mediated phosphorylation of HACE1 at serine 385 regulates its oligomerization state and Rac1 ubiquitination
Authors: Acosta Maria I. , Urbach Serge , Doye Anne , Ng Yuen-Wai , Boudeau Jérôme , Mettouchi Amel , Debant Anne , Manser Edward , Visvikis Orane , Lemichez Emmanuel 
Published: January 2018

AbstractThe regulation of Rac1 by HACE1-mediated ubiquitination and proteasomal degradation is emerging as an essential element in the maintenance of cell homeostasis. However, how the E3 ubiquitin ligase activity of HACE1 is regulated remains undetermined. Using a proteomic approach, we identified serine 385 as a target of group-I PAK kinases downstream Rac1 activation by CNF1 toxin from pathogenic E. coli. Moreover, cell treatment with VEGF also promotes Ser-385 phosphorylation of HACE1. We have established in vitro that HACE1 is a direct target of PAK1 kinase activity. Mechanistically, we found that the phospho-mimetic mutant HACE1(S385E), as opposed to HACE1(S385A), displays a lower capacity to ubiquitinate Rac1 in cells. Concomitantly, phosphorylation of Ser-385 plays a pivotal role in controlling the oligomerization state of HACE1. Finally, Ser-385 phosphorylated form of HACE1 localizes in the cytosol away from its target Rac1. Together, our data point to a feedback inhibition of HACE1 ubiquitination activity on Rac1 by group-I PAK kinases.
Fahrtauglichkeit bei Leichter Kognitiver Störung und Demenz
Authors: Schmidtke Klaus 
Published: January 2018

ZusammenfassungExekutive Leistungen, visuell-räumliches Denken und Verhaltenskontrolle sind für das sichere Autofahren wesentliche geistige Leistungen. Bei
Demenz und Leichter Kognitiver Störung treten Defizite dieser Leistungen auf, die sich zu altersbedingten Defiziten addieren. Sie können
durch eine angepasste Fahrweise nicht immer ausreichend kompensiert werden und führen ggf. schon im frühen Stadium zur Aufhebung der
Fahrtauglichkeit. Neurologen und Psychiater kommt eine wichtige Rolle bei der Untersuchung, Aufklärung und ggf. Aussprache eines ärztlichen
Fahrverbotes zu. Fehler und Unterlassungen können hier unter Umständen juristische Konsequenzen nach sich ziehen. Der vorliegende Beitrag
stellt die relevanten Erkrankungen und die mit ihnen assoziierten kognitiven Störungen dar, gibt Empfehlungen für die neuropsychologische
Untersuchung und die Kommunikation mit Patienten und Angehörigen.
PAR1 agonists stimulate APC-like endothelial cytoprotection and confer resistance to thromboinflammatory injury
Authors: De Ceunynck Karen , Peters Christian G. , Jain Abhishek , Higgins Sarah J. , Aisiku Omozuanvbo , Fitch-Tewfik Jennifer L. , Chaudhry Sharjeel A. , Dockendorff Chris , Parikh Samir M. , Ingber Donald E. , Flaumenhaft Robert 
Published: January 2018

Significance
Protease-activated receptors (PARs) are G-protein–coupled receptors (GPCRs) that are activated by proteolysis and couple to multiple distinct G-proteins. Cleavage of PAR1 in endothelium stimulates either proinflammatory or antiinflammatory signaling depending on the activating protease and is important in thrombosis and inflammation. Yet the biased signaling of PAR1 has made its pharmacological modulation challenging. We show that a family of compounds, parmodulins, acts at the cytosolic face of PAR1 to differentially control G-protein coupling and stimulate cytoprotective signaling while blocking deleterious signaling. Parmodulins are antiinflammatory and antithrombotic in vivo. These compounds demonstrate the utility of targeting the cytosolic face of GPCRs to selectively modulate downstream signaling and could provide an alternative for treatment of thromboinflammatory disorders.
DExSI: a new tool for the rapid quantitation of 13C-labelled metabolites detected by GC-MS
Authors: Dagley Michael J , McConville Malcolm J 
Published: January 2018

Abstract

Summary
Stable isotope directed metabolomics is increasingly being used to measure metabolic fluxes in microbial, plant and animal cells. Incorporation of 13C/15N isotopes into a wide range of metabolites is typically determined using gas chromatography-mass spectrometry (GC/MS) or other hyphenated mass spectrometry approaches. The DExSI (Data Extraction for Stable Isotope-labelled metabolites) pipeline is an interactive graphical software package which can be used to rapidly quantitate isotopologues for a wide variety of metabolites detected by GC/MS. DExSI performs automated metabolite annotation, mass and positional isotopomer abundance determination and natural isotope abundance correction. It provides a range of output options and is suitable for high throughput analyses.

Availability and implementation
DExSI is available for non-commercial use from: https://github.com/DExSI/DExSI/. For Microsoft Windows 7 or higher (64-bit).

Supplementary information
Supplementary data are available at Bioinformatics online.
CHRONIC CENTRAL SEROUS CHORIORETINOPATHY
Authors: Iacono Pierluigi , Tedeschi Massimiliano , Boccassini Barbara , Chiaravalloti Adele , Varano Monica , Parravano Mariacristina 
Published: January 2018

Purpose:
To describe early and late morphological and functional changes in subjects receiving photodynamic therapy (PDT) for chronic central serous chorioretinopathy.

Methods:
Patients with chronic central serous chorioretinopathy were prospectively enrolled and received standard PDT. At the baseline examination, each subject underwent complete ophthalmological examination, including best-corrected visual acuity (BCVA) assessment, fluorescein angiography and indocyanine green angiography, spectral domain optical coherence tomography, and microperimetry. Spectral domain optical coherence tomography, microperimetry, and BCVA assessment were repeated in multiple sections over 7 days after PDT and at 1-, 3-, and 12-month intervals. Main outcome measures were: identification of early changes (1-week examination) in BCVA, retinal sensitivity, and spectral domain optical coherence tomography parameters and their influence on outcomes at the 1-year follow-up.

Results:
Three main patterns of early response to PDT were identified during the 1-week examination. The neurosensory retinal detachment most frequently decreased rapidly (12/19 pts), with complete resolution in 50% of cases. An increase in neurosensory retinal detachment height was registered in 16% (3/19) of cases, whereas in 21% (4/19), a large fluctuation in neurosensory retinal detachment was encountered. Best-corrected visual acuity declined significantly in 5/12 patients in the first group and was stable or improved in the remaining cases. Overall, retinal sensitivity diminished in 16/19 subjects, with a mean worsening of 2.56 dB (P = 0.0002). At the 12-month examination, final mean BCVA improved by 14.4 letters (P = 0.001) and a similar progressive recovery in the retinal sensitivity was observed (+2.69 dB, P = 0.0039). The neurosensory retinal detachment completely resolved in 18/19 (95%) cases, with a parallel significant reduction in central foveal choroidal thickness (P < 0.0001).

Conclusion:
Three patterns of early response to standard PDT can be identified. Although an early and abrupt reduction in BCVA and retinal sensitivity after treatment is possible, this does not compromise a final improvement in visual functions.
COMPARING FUNDUS FLUORESCEIN ANGIOGRAPHY AND SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN THE EVALUATION OF DIABETIC MACULAR PERFUSION
Authors: La Mantia Alberto , Kurt Rengin A. , Mejor Samantha , Egan Catherine A. , Tufail Adnan , Keane Pearse A. , Sim Dawn A. 
Published: January 2018

Purpose:
To compare fundus fluorescein angiography (FFA) and swept-source optical coherence tomography angiography (SS-OCTA) in the evaluation of macular perfusion in diabetic patients.

Methods:
Forty-one eyes (21 diabetic patients) seen at Moorfields Eye Hospital (London) over a 1-month interval underwent color fundus photography, FFA, and SS-OCTA imaging of the capillary superficial plexus using 2 different protocols: 3 × 3 mm and 4.5 × 4.5 mm. Quantitative assessment (foveal avascular zone diameters and area), qualitative analysis (macroscopic and microscopic levels) and Early Treatment Diabetic Retinopathy Study diabetic macular ischemia grading were performed. Artifacts were recorded. Intraclass correlation coefficients and weighted kappa values were calculated.

Results:
Mean (SD) foveal avascular zone area was 0.695 (0.52) mm2 on FFA, 0.627 (0.54) mm2 on SS-OCTA 3 × 3 and 0.701 (0.54) mm2 on SS-OCTA 4.5 × 4.5 protocol. Intraclass correlation coefficients showed good agreement between FFA and SS-OCTA for both vertical diameter and foveal avascular zone area measurements. The agreement between SS-OCTA 3 × 3 and 4.5 × 4.5 was good for all quantitative measurements. Weighted kappa for diabetic macular ischemia grading showed low to fair agreement between FFA and SS-OCTA, whereas the agreement was good between two different SS-OCTA protocols.

Conclusion:
Swept-source OCTA is a reproducible technique in the assessment of macular perfusion in diabetic patients with special regards to foveal avascular zone analysis. The agreement with FFA is limited especially for diabetic macular ischemia grading. Fundus fluorescein angiography is more sensitive in identifying microaneurysms.
An overview of confounding. Part 2: how to identify it and special situations
Authors: Howards Penelope P. 
Published: January 2018

AbstractConfounding biases study results when the effect of the exposure on the outcome mixes with the effects of other risk and protective factors for the outcome that are present differentially by exposure status. However, not all differences between the exposed and unexposed group cause confounding. Thus, sources of confounding must be identified before they can be addressed. Confounding is absent in an ideal study where all of the population of interest is exposed in one universe and is unexposed in a parallel universe. In an actual study, an observed unexposed population represents the unobserved parallel universe. Thinking about differences between this substitute population and the unexposed parallel universe helps identify sources of confounding. These differences can then be represented in a diagram that shows how risk and protective factors for the outcome are related to the exposure. Sources of confounding identified in the diagram should be addressed analytically and through study design. However, treating all factors that differ by exposure status as confounders without considering the structure of their relation to the exposure can introduce bias. For example, conditions affected by the exposure are not confounders. There are also special types of confounding, such as time‐varying confounding and unfixable confounding. It is important to evaluate carefully whether factors of interest contribute to confounding because bias can be introduced both by ignoring potential confounders and by adjusting for factors that are not confounders. The resulting bias can result in misleading conclusions about the effect of the exposure of interest on the outcome.
Apoptosis induction in K562 human myelogenous leukaemia cells is connected to the modulation of Wnt/β‐catenin signalling by BHX, a novel pyrazoline derivative
Authors: Bao Hanmei , Zhang Qing , Du Yibo , Zhang Cai , Xu Hui , Zhu Zhongling , Yan Zhao 
Published: January 2018

AbstractObjectivesThe goal of this study was to explore the effects of BHX on human chronic myeloid leukaemia (CML) cells and to elucidate the underlying molecular mechanism.Materials and methodsCML cell line K562 cells were treated with BHX. The effects of BHX on cell proliferation, apoptosis and cell cycle were detected. Subsequently, the caspase, ATP activity, Ca2+, ROS and mitochondrial membrane potential (MMP) levels treated with various concentrations of BHX were analysed. The variation of relevant proteins and genes was detected. Further, toxicity of BHX on peripheral blood cells, bone marrow‐nucleated cells (BMNC) and organ index were investigated on mice.ResultsResults showed that BHX suppressed K562 cell proliferation in a dose‐dependent manner and induced apoptosis and G0/G1 phase arrest. BHX induced mitochondria‐mediated apoptosis, which was associated with downregulation of MMP, activation of caspase‐3 and caspase‐9, generation of intracellular ROS and elevation of Ca2+ in K562 cells. In treated cells, ATP levels were decreased, expression of total β‐catenin, phosphorylated β‐catenin and β‐catenin in the nucleus was decreased, and expression of cell cycle‐related proteins was decreased. Further analysis revealed that BHX lowered the transcriptional level of β‐catenin. Lastly, BHX treatment significantly reduced the number of white blood cells, but had no effect on BMNC and organ index.ConclusionsThese findings provide further insight into the potential use of BHX as an anti‐cancer agent against human leukaemia.
Nest box design for a changing climate: The value of improved insulation
Authors: Larson Eliza R. , Eastwood Justin R. , Buchanan Katherine L. , Bennett Andrew T. D. , Berg Mathew L. 
Published: January 2018

SummaryMean air temperatures and the frequency, intensity and duration of extreme weather events such as heatwaves are increasing due to climate change. Nest boxes experience more variable and extreme temperatures than natural cavities, which may reduce survival and reproductive success of the species which utilize them, but little is known about the factors which drive nest box temperature profiles. We quantified the potential for retrofitted insulation on nest boxes to modify internal temperatures and to mimic the thermal characteristics of natural cavities more closely. We tested three types of materials with insulative or reflective properties which were easy to retrofit to nest boxes: 3‐cm‐thick polystyrene, pleated foil batts and reflective paint. We found that polystyrene and foil batts reduced mean nest box temperatures during the day by 0.31 ± 0.01°C and 0.17 ± 0.01°C, respectively (but up to 5.84°C and 4.02°C). The effects of all insulation types were dependent on the time of day, and only polystyrene had a significant effect at night, with a greater capacity to retain heat (mean 0.21 ± 0.01°C warmer). Contrary to expectations, reflective paint caused a small increase in temperature during the late afternoon. In our study, the temperature modulation provided by insulation was able to match or exceed that due to variation in nest location and surrounding vegetation canopy cover. Our findings show that polystyrene and foil batts may offer effective and tractable means to mitigate the effects of extreme temperatures in nest boxes and thereby help achieve temperature profiles more similar to natural cavities.
Honest error, precaution or alertness advertisement? Reactions to vertebrate pseudopredators in red‐nosed cuxiús (Chiropotes albinasus),a high‐canopy neotropical primate
Authors: Barnett Adrian A. , de Oliveira Tadeu , Soares da Silva Rafaela Fatima , de Albuquerque Teixeira Samara , Tomanek Pavel , Todd Lucy M. , Boyle Sarah A. 
Published: January 2018

AbstractPredation on primates is considered to have far‐reaching effects on the foraging and social ecology of a species. Primate species display a variety of responses to predator proximity and attack, ranging from active physical defense and mobbing, to flight and concealment. Warning calls are often given, and potentially threatening animals may be tracked, either actively or with head movements. Such behaviors take time that could be used for other activities. Accordingly, there should be strong selection to respond only to those species that represent a genuine threat. However, primates give defense‐based behaviors to non‐predator species. We tested the hypotheses that responses to pseudopredators are (i) precautionary calls made by individuals following the Dinner/Life Principle, or (ii) represent the ontogeny of species recognition. Of the species that ellicted a response from the cuxiús, 80% resembled a primate predator; 95% of the encounters that elicited a response from the cuxiús occurred when the distance between the pseudopredator and cuxiús was ≤20 m. In regard to the frequency of responses to pseudopredators, we found no difference between adults and juveniles (47.6% and 52.4%, respectively) and no differences between adult males and adult females (60% and 40% of the responses, respectively). However, reactions to pseudopredators were of shorter duration ( ± standard error (SE): 42.2 ± 15.9 s) than were reactions to actual predator species ( ± SE: 1,024.3 ± 329.1 s). There were only three instances where alarm calls were made to species that did not resemble predators, and 66.7% (N = 2) were made by adult cuxiús and only 33.3% (N = 1) were made by a juvenile cuxiú. Therefore, we found partial support for the Dinner/Life Principle hypothesis, but no support for the ontogeny hypothesis. Examination of such responses to pseudopredators in other primate and non‐primate species may help understand the evolution of such behaviors.
The development and validation of the Evidence‐Based Practice Questionnaire: Japanese version
Authors: Tomotaki Ai , Fukahori Hiroki , Sakai Ikuko , Kurokohchi Kana 
Published: January 2018

AbstractAimTo develop and test the validity and reliability of a Japanese version of the Evidence‐Based Practice Questionnaire.MethodsThe Evidence‐Based Practice Questionnaire was translated into Japanese, and a back‐translation was performed. In March 2016, the survey was conducted among 843 nurses in 2 university hospitals in Japan. After 2 weeks, the same questionnaire for test‐retest reliability was distributed to 197 nurses. We evaluated construct validity by factor analysis: convergent, discriminant, criterion‐based and known‐group validity, and reliability (internal consistency via Cronbach' alpha and test‐retest reliability).ResultsA total of 533 (66%) of nurses who agreed to our study returned the completed questionnaire, and 108 nurses (55%) agreed to the test‐retest. Factor analysis confirmed that the original model of the Evidence‐Based Practices Questionnaire was not statistically appropriate for Japanese nurses. Therefore, the final version of the Japanese version adopted 18 items and 4 subscales including practice, attitudes, and knowledge/skills related to research and practice. In the final version, the validity and reliability were moderate (Cronbach alpha = .90).ConclusionThe Japanese version of the Evidence‐Based Practices Questionnaire is a reliable and valid tool and can be used to assess evidence‐based practice, attitudes, and research knowledge/skills in Japan.
Current knowledge of nocardiosis in teleost fish
Authors: Maekawa S , Yoshida T , Wang P‐C , Chen S‐C 
Published: January 2018

AbstractNocardia sp. is the causative agent of nocardiosis, a lethal granulomatous disease of the skin, muscle, and various inner tissues affecting various teleost and shellfish. Four species of Nocardia have been isolated from diseased fish and shellfish, namely Nocardia asteroides, Nocardia seriolae, Nocardia salmonicida and Nocardia crassostreae. Therefore, in fish aquaculture, nocardiosis has caused severe economic losses, especially in the Asian region. Considerable research has been performed, since the first report of identified Nocardia sp. in fish, to characterize Nocardia sp. and identify rapid detection techniques, immune response against infection and prophylactic approaches. In this review, the current state of knowledge about nocardiosis in fish has been presented, including the pathogenesis, diagnosis, host immune response and vaccine development.
A mutation in the heptad repeat 2 domain of MFN2 in a large CMT2A family
Authors: Dankwa Lois , Richardson Jessica , Motley William W. , Züchner Stephan , Scherer Steven S. 
Published: January 2018

AbstractDominant mutations in MFN2 cause a range of phenotypes, including severe, early‐onset axonal neuropathy, “classical CMT2,” and late‐onset axonal neuropathies. We report a large family with an axonal polyneuropathy, with clinical onset in the 20s, followed by slow progression.
Chronic sleep reduction in adolescents—clinical cut‐off scores for the Chronic Sleep Reduction Questionnaire (CSRQ)
Authors: Dewald‐Kaufmann Julia F. , Bruin Eduard J. , Smits Marcel , Zijlstra Bonne J.H. , Oort Frans J. , Meijer Anne Marie 
Published: January 2018

SummaryThe Chronic Sleep Reduction Questionnaire is a validated questionnaire that measures symptoms of prolonged insufficient and/or poor sleep and therefore accounts for individuals’ sleep need and sleep debt. This study extends its psychometric properties by providing cut‐off scores, using a matched sample of 298 healthy adolescents (15.38 ± 1.63 years, 37.9% male, mean Chronic Sleep Reduction Questionnaire score: 32.98 ± 6.51) and 298 adolescents with insomnia/delayed sleep–wake phase disorder (15.48 ± 1.62 years; 37.9% male, mean Chronic Sleep Reduction Questionnaire score: 42.59 ± 7.06). We found an area under the curve of 0.84 (95% confidence interval: 0.81–0.87). Cut‐off scores for optimal sensitivity, optimal specificity and based on Youden's criterion are provided. These cut‐off scores are highly relevant for use of the Chronic Sleep Reduction Questionnaire in future studies and clinical practice.