bluuebunny/crossref_metadata_2025_split huggingface dataset:
CETSA-based target engagement of taxanes as biomarkers for efficacy and resistance
Authors: Langebäck Anette , Bacanu Smaranda , Laursen Henriette , Mout Lisanne , Seki Takahiro , Erkens-Schulze Sigrun , Ramos Anderson Daniel , Berggren Anna , Cao Yihai , Hartman Johan , van Weerden Wytske , Bergh Jonas , Nordlund Pär , Lööf Sara 
Published: December 2019

AbstractThe use of taxanes has for decades been crucial for treatment of several cancers. A major limitation of these therapies is inherent or acquired drug resistance. A key to improved outcome of taxane-based therapies is to develop tools to predict and monitor drug efficacy and resistance in the clinical setting allowing for treatment and dose stratification for individual patients. To assess treatment efficacy up to the level of drug target engagement, we have established several formats of tubulin-specific Cellular Thermal Shift Assays (CETSAs). This technique was evaluated in breast and prostate cancer models and in a cohort of breast cancer patients. Here we show that taxanes induce significant CETSA shifts in cell lines as well as in animal models including patient-derived xenograft (PDX) models. Furthermore, isothermal dose response CETSA measurements allowed for drugs to be rapidly ranked according to their reported potency. Using multidrug resistant cancer cell lines and taxane-resistant PDX models we demonstrate that CETSA can identify taxane resistance up to the level of target engagement. An imaging-based CETSA format was also established, which in principle allows for taxane target engagement to be accessed in specific cell types in complex cell mixtures. Using a highly sensitive implementation of CETSA, we measured target engagement in fine needle aspirates from breast cancer patients, revealing a range of different sensitivities. Together, our data support that CETSA is a robust tool for assessing taxane target engagement in preclinical models and clinical material and therefore should be evaluated as a prognostic tool during taxane-based therapies.
RETRACTED ARTICLE: The diagnostic nomogram of platelet-based score models for
hepatic alveolar echinococcosis and atypical liver cancer
Authors: Du Qiancheng , Wang Yanyan , Guan Shihao , Hu Chenliang , Li Mengxuan , Zhou Ling , Zhang Mengzhao , Chen Yichong , Mei Xuepeng , Sun Jian , Zhou Ying 
Published: December 2019

AbstractHepatic alveolar echinococcosis (HAE) and liver cancer had similarities
in imaging results, clinical characteristics, and so on. And it is difficult for
clinicians to distinguish them before operation. The aim of our study was to build a
differential diagnosis nomogram based on platelet (PLT) score model and use internal
validation to check the model. The predicting model was constructed by the
retrospective database that included in 153 patients with HAE (66 cases) or liver
cancer (87 cases), and all cases was confirmed by clinicopathology and collected
from November 2011 to December 2018. Lasso regression analysis model was used to
construct data dimensionality reduction, elements selection, and building prediction
model based on the 9 PLT-based scores. A multi-factor regression analysis was
performed to construct a simplified prediction model, and we added the selected
PLT-based scores and relevant clinicopathologic features into the nomogram.
Identification capability, calibration, and clinical serviceability of the
simplified model were evaluated by the Harrell’s concordance index (C-index),
calibration plot, receiver operating characteristic curve (ROC), and decision curve.
An internal validation was also evaluated by the bootstrap resampling. The
simplified model, including in 4 selected factors, was significantly associated with
differential diagnosis of HAE and liver cancer. Predictors of the simplified
diagnosis nomogram consisted of the API index, the FIB-4 index, fibro-quotent
(FibroQ), and fibrosis index constructed by King’s College Hospital (King’s score).
The model presented a perfect identification capability, with a high C-index of
0.929 (0.919 through internal validation), and good calibration. The area under the
curve (AUC) values of this simplified prediction nomogram was 0.929, and the result
of ROC indicated that this nomogram had a good predictive value. Decision curve
analysis showed that our differential diagnosis nomogram had clinically
identification capability. In conclusion, the differential diagnosis nomogram could
be feasibly performed to verify the preoperative individualized diagnosis of HAE and
liver cancer.
A novel, sensitive dual-indicator cell line for detection and quantification of inducible, replication-competent latent HIV-1 from reservoir cells
Authors: Salasc Fanny , Gludish David W. , Jarvis Isobel , Boliar Saikat , Wills Mark R. , Russell David G. , Lever Andrew M. L. , Mok Hoi-Ping 
Published: December 2019

AbstractUnderstanding the mechanisms involved in HIV infection and latency, and development of a cure, rely on the availability of sensitive research tools such as indicator cells, which allow rigorous quantification of viral activity. Here we describe the construction and validation of a novel dual-indicator cell line, Sup-GGR, which offers two different readouts to quantify viral replication. A construct expressing both Gaussia luciferase and hrGFP in a Tat- and Rev-dependent manner was engineered into SupT1-CCR5 to create Sup-GGR cells. This cell line supports the replication of both X4 and R5-tropic HIV as efficiently as its parental cell line, SupT1-CCR5, and allows repeated sampling without the need to terminate the culture. Sup-GGR demonstrates comparable sensitivity and similar kinetics in virus outgrowth assays (VOA) to SupT1-CCR5 using clinical samples. However the Gaussia luciferase reporter is significantly less labor-intensive and allows earlier detection of reactivated latent viruses compared to the conventional HIV p24 ELISA assay. The Sup-GGR cell line constitutes a versatile new tool for HIV research and clinical trials.
Tuning of ionic mobility to improve the resistive switching behavior of Zn-doped CeO2
Authors: Rehman Shania , Kim Honggyun , Farooq Khan Muhammad , Hur Ji-Hyun , Lee Anthony D. , Kim Deok-kee 
Published: December 2019

AbstractCorrelation between the resistive switching characteristics of Au/Zn-doped CeO2/Au devices and ionic mobility of CeO2 altered by the dopant concentration were explored. It was found that the ionic mobility of CeO2 has a profound effect on the operating voltages of the devices. The magnitude of operating voltage was observed to decrease when the doping concentration of Zn was increased up to 14%. After further increasing the doping level to 24%, the device hardly exhibits any resistive switching. At a low doping concentration, only isolated Vo existed in the CeO2 lattice. At an intermediate doping concentration, the association between dopant and Vo formed (Zn, Vo)× defect clusters. Low number density of these defect clusters initially favored the formation of Vo filament and led to a reduction in operating voltage. As the size and number density of (Zn, Vo)× defect clusters increased at a higher doping concentration, the ionic conductivity was limited with the trapping of isolated Vo by these defect clusters, which resulted in the diminishing of resistive switching. This research work provides a strategy for tuning the mobility of Vo to modulate resistive switching characteristics for non-volatile memory applications.
Sensitivity and specificity of metatranscriptomics as an arbovirus surveillance tool
Authors: Batovska Jana , Mee Peter T. , Lynch Stacey E. , Sawbridge Tim I. , Rodoni Brendan C. 
Published: December 2019

AbstractThe ability to identify all the viruses within a sample makes metatranscriptomic sequencing an attractive tool to screen mosquitoes for arboviruses. Practical application of this technique, however, requires a clear understanding of its analytical sensitivity and specificity. To assess this, five dilutions (1:1, 1:20, 1:400, 1:8,000 and 1:160,000) of Ross River virus (RRV) and Umatilla virus (UMAV) isolates were spiked into subsamples of a pool of 100 Culex australicus mosquitoes. The 1:1 dilution represented the viral load of one RRV-infected mosquito in a pool of 100 mosquitoes. The subsamples underwent nucleic acid extraction, mosquito-specific ribosomal RNA depletion, and Illumina HiSeq sequencing. The viral load of the subsamples was also measured using reverse transcription droplet digital PCR (RT-ddPCR) and quantitative PCR (RT-qPCR). Metatranscriptomic sequencing detected both RRV and UMAV in the 1:1, 1:20 and 1:400 subsamples. A high specificity was achieved, with 100% of RRV and 99.6% of UMAV assembled contigs correctly identified. Metatranscriptomic sequencing was not as sensitive as RT-qPCR or RT-ddPCR; however, it recovered whole genome information and detected 19 other viruses, including four first detections for Australia. These findings will assist arbovirus surveillance programs in utilising metatranscriptomics in routine surveillance activities to enhance arbovirus detection.
Systematic Modification of Zingerone Reveals Structural Requirements for Attraction of Jarvis’s Fruit Fly
Authors: Hanssen Benjamin L. , Park Soo Jean , Royer Jane E. , Jamie Joanne F. , Taylor Phillip W. , Jamie Ian M. 
Published: December 2019

AbstractTephritid fruit flies are amongst the most significant horticultural pests globally and male chemical lures are important for monitoring and control. Zingerone has emerged as a unique male fruit fly lure that can attract dacine fruit flies that are weakly or non-responsive to methyl eugenol and cuelure. However, the key features of zingerone that mediate this attraction are unknown. As Jarvis’s fruit fly, Bactrocera jarvisi (Tryon), is strongly attracted to zingerone, we evaluated the response of B. jarvisi to 37 zingerone analogues in a series of field trials to elucidate the functional groups involved in attraction. The most attractive analogues were alkoxy derivatives, with isopropoxy being the most attractive, followed by ethoxy and trifluoromethoxy analogues. All of the phenolic esters tested were also attractive with the response typically decreasing with increasing size of the ester. Results indicate that the carbonyl group, methoxy group, and phenol of zingerone are key sites for the attraction of B. jarvisi and identify some constraints on the range of structural modifications that can be made to zingerone without compromising attraction. These findings are important for future work in developing and optimising novel male chemical lures for fruit flies.
Revision surgery after triple semicircular canal plugging and morphologic changes of vestibular organ
Authors: Zhang Daogong , Lv Yafeng , Han Yuechen , Sun Gaoying , Li Yawei , Li Xiaofei , Sun Lixin , Gong Ruozhen , Fan Zhaomin , Wang Haibo 
Published: December 2019

AbstractThis study aims to investigate the causes of vertigo relapse in patients with Meniere’s disease (MD) who had undergone triple semicircular canal plugging (TSCP) and explore the morphologic changes of vestibular organ through revision surgery. Eleven intractable MD patients who underwent TSCP initially and experienced episodic vertigo recurrence later, were enrolled. All patients accepted revision surgery, including seven cases who underwent labyrinthectomy and four cases who underwent repeat TSCP. Pure tone test, caloric test and video-head impulse test (v-HIT) were used to evaluate audiological and vestibular functions. Specimens of canal plugging materials and vestibular end organs were collected from patients who underwent labyrinthectomy during revision surgery. Mineralization and other histological characteristics of canal plugging materials were evaluated by von Kossa staining. Incomplete occlusion or ossification was observed in the semicircular canals (SCs) of all eleven patients, with all three SCs affected in three, the superior SC in five patients, the horizontal SC in two and the posterior SC in one. The results of v-HIT were in accordance with findings discovered intraoperatively. Few mineralized nodules and multiple cavities were found in the von Kossa-stained canal plugging materials. Incomplete occlusion or ossification of SCs was the principal cause of vertigo recurrence in MD patients who underwent TSCP. v-HIT was helpful in determining the responsible SCs.
Outcome contingency selectively affects the neural coding of outcomes but not of tasks
Authors: Wisniewski David , Forstmann Birte , Brass Marcel 
Published: December 2019

AbstractValue-based decision-making is ubiquitous in every-day life, and critically depends on the contingency between choices and their outcomes. Only if outcomes are contingent on our choices can we make meaningful value-based decisions. Here, we investigate the effect of outcome contingency on the neural coding of rewards and tasks. Participants performed a reversal-learning paradigm in which reward outcomes were contingent on trial-by-trial choices, and performed a ‘free choice’ paradigm in which rewards were random and not contingent on choices. We hypothesized that contingent outcomes enhance the neural coding of rewards and tasks, which was tested using multivariate pattern analysis of fMRI data. Reward outcomes were encoded in a large network including the striatum, dmPFC and parietal cortex, and these representations were indeed amplified for contingent rewards. Tasks were encoded in the dmPFC at the time of decision-making, and in parietal cortex in a subsequent maintenance phase. We found no evidence for contingency-dependent modulations of task signals, demonstrating highly similar coding across contingency conditions. Our findings suggest selective effects of contingency on reward coding only, and further highlight the role of dmPFC and parietal cortex in value-based decision-making, as these were the only regions strongly involved in both reward and task coding.
Species richness and vulnerability to disturbance propagation in real food webs
Authors: Calizza Edoardo , Rossi Loreto , Careddu Giulio , Sporta Caputi Simona , Costantini Maria Letizia 
Published: December 2019

AbstractA central issue in ecology is understanding how complex and biodiverse food webs persist in the face of disturbance, and which structural properties affect disturbance propagation among species. However, our comprehension of assemblage mechanisms and disturbance propagation in food webs is limited by the multitude of stressors affecting ecosystems, impairing ecosystem management. By analysing directional food web components connecting species along food chains, we show that increasing species richness and constant feeding linkage density promote the establishment of predictable food web structures, in which the proportion of species co-present in one or more food chains is lower than what would be expected by chance. This reduces the intrinsic vulnerability of real food webs to disturbance propagation in comparison to random webs, and suggests that biodiversity conservation efforts should also increase the potential of ecological communities to buffer top-down and bottom-up disturbance in ecosystems. The food web patterns observed here have not been noticed before, and could also be explored in non-natural networks.
Automated quantification of synaptic boutons reveals their 3D distribution in the honey bee mushroom body
Authors: Cabirol Amélie , Haase Albrecht 
Published: December 2019

AbstractSynaptic boutons are highly plastic structures undergoing experience-dependent changes in their number, volume, and shape. Their plasticity has been intensively studied in the insect mushroom bodies by manually counting the number of boutons in small regions of interest and extrapolating this number to the volume of the mushroom body neuropil. Here we extend this analysis to the synaptic bouton distribution within a larger subregion of the mushroom body olfactory neuropil of honey bees (Apis mellifera). This required the development of an automated method combining two-photon imaging with advanced image post-processing and multiple threshold segmentation. The method was first validated in subregions of the mushroom body olfactory and visual neuropils. Further analyses in the olfactory neuropil suggested that previous studies overestimated the number of synaptic boutons. As a reason for that, we identified boundaries effects in the small volume samples. The application of the automated analysis to larger volumes of the mushroom body olfactory neuropil revealed a corrected average density of synaptic boutons and, for the first time, their 3D spatial distribution. This distribution exhibited a considerable heterogeneity. This additional information on the synaptic bouton distribution provides the basis for future studies on brain development, symmetry, and plasticity.
N-Octanoyl-Dopamine inhibits cytokine production in activated T-cells and diminishes MHC-class-II expression as well as adhesion molecules in IFNγ-stimulated endothelial cells
Authors: Hofmann Björn B. , Krapp Nicolas , Li Yingchun , De La Torre Carolina , Sol Marloes , Braun Jana D. , Kolibabka Matthias , Pallavi Prama , Krämer Bernhard K. , Yard Benito A. , Kälsch Anna-Isabelle 
Published: December 2019

AbstractIFNγ enhances allograft immunogenicity and facilitates T-cell mediated rejection. This may cause interstitial fibrosis and tubular atrophy (IFTA), contributing to chronic allograft loss. We assessed if inhibition of T-cell activation by N-octanoyl dopamine (NOD) impairs adherence of activated T-cells to endothelial cells and the ability of activated T-cells to produce IFNγ. We also assessed if NOD affects IFNγ mediated gene expression in endothelial cells. The presence of NOD during T-cell activation significantly blunted their adhesion to unstimulated and cytokine stimulated HUVEC. Supernatants of these T-cells displayed significantly lower concentrations of TNFα and IFNγ and were less capable to facilitate T-cell adhesion. In the presence of NOD VLA-4 (CD49d/CD29) and LFA-1 (CD11a/CD18) expression on T-cells was reduced. NOD treatment of IFNγ stimulated HUVEC reduced the expression of MHC class II transactivator (CIITA), of MHC class II and its associated invariant chain CD74. Since IFTA is associated with T-cell mediated rejection and IFNγ to a large extent regulates immunogenicity of allografts, our current data suggest a potential clinical use of NOD in the treatment of transplant recipients. Furtherin vivostudies are warranted to confirm thesein vitrofindings and to assess the benefit of NOD on IFTA in clinically relevant models.
A causal relationship between cigarette smoking and type 2 diabetes mellitus: A Mendelian randomization study
Authors: Yuan Shuai , Larsson Susanna C. 
Published: December 2019

AbstractThe causality between smoking and type 2 diabetes is unclear. We conducted a two-sample Mendelian randomization study to explore the causal relationship between smoking initiation and type 2 diabetes. Summary-level data for type 2 diabetes were obtained from a meta-analysis of 32 genome-wide association studies (DIAbetes Genetics Replication And Meta-analysis consortium), which included 898 130 individuals of European ancestry. Totally, 377 single-nucleotide polymorphisms associated with smoking initiation at genome wide significance threshold (p < 5 × 10−8) were identified from the hitherto largest genome-wide association study on smoking. The inverse-variance weighted, weighted median, MR-Egger regression, and MR-PRESSO approaches were used to analyze the data. Genetically predicted smoking initiation was associated with type 2 diabetes with an odds ratio of 1.28 (95% confidence interval, 1.20, 1.37; p = 2.35 × 10−12). Results were consistent across sensitivity analyses and there was no evidence of horizontal pleiotropy. This study provides genetic evidence supporting a causal association between the smoking initiation and type 2 diabetes. Reducing cigarette smoking initiation can now be even more strongly recommended for type 2 diabetes prevention.
Physiological traits determining high adaptation potential of sweet briar (Rosa rubiginosa L.) at early stage of growth to dry lands
Authors: Gadzinowska Joanna , Ostrowska Agnieszka , Hura Katarzyna , Dziurka Michał , Pawłowska Bożena , Hura Tomasz 
Published: December 2019

AbstractLittle is known about mechanisms of sweet briar adaptation to dry habitats. The species is highly invasive and displaces native plants from dry lands of the southern hemisphere. This study evaluates physiological basis of Rosa rubiginosa L. adaptation to soil drought. We performed a pot soil drought experiment and assessed water relations, water use efficiency, gas exchange and photosynthetic apparatus activity. The study also measured the content of chlorophyll, soluble carbohydrates and proline and analyzed plant biomass growth. We hypothesized that the drought stress induced an effective mechanism enabling adaptation of young sweet briar roses to soil water deficit. The study identified several adaptation mechanisms of R. rubiginosa allowing the plant to survive soil drought. These included limiting transpiration and stomatal conductance, increasing the level of soluble sugars, reducing chlorophyll content, accumulating CO2 in intercellular spaces, and increasing the quantum yield of electron transport from QA− to the PSI end electron acceptors. As a result, young sweet briar roses limited water loss and photoinhibition damage to the photosynthetic apparatus, which translated into consumption of soluble sugars for growth purposes. This study showed that photosynthesis optimization and increased activity of the photosynthetic apparatus made it possible to avoid photoinhibition and to effectively use water and sugars to maintain growth during water stress. This mechanism is probably responsible for the invasive nature of R. rubiginosa and its huge potential to displace native plant species from dry habitats of the southern hemisphere.
Inhibition of epileptiform activity by neuropeptide Y in brain tissue from drug-resistant temporal lobe epilepsy patients
Authors: Wickham Jenny , Ledri Marco , Bengzon Johan , Jespersen Bo , Pinborg Lars H. , Englund Elisabet , Woldbye David P. D. , Andersson My , Kokaia Merab 
Published: December 2019

AbstractIn epilepsy patients, drug-resistant seizures often originate in one of the temporal lobes. In selected cases, when certain requirements are met, this area is surgically resected for therapeutic reasons. We kept the resected tissue slices alive in vitro for 48 h to create a platform for testing a novel treatment strategy based on neuropeptide Y (NPY) against drug-resistant epilepsy. We demonstrate that NPY exerts a significant inhibitory effect on epileptiform activity, recorded with whole-cell patch-clamp, in human hippocampal dentate gyrus. Application of NPY reduced overall number of paroxysmal depolarising shifts and action potentials. This effect was mediated by Y2 receptors, since application of selective Y2-receptor antagonist blocked the effect of NPY. This proof-of-concept finding is an important translational milestone for validating NPY-based gene therapy for targeting focal drug-resistant epilepsies, and increasing the prospects for positive outcome in potential clinical trials.