bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective Effects of Thioridazine on Self-Renewal of Basal-Like Breast Cancer Cells
Authors: Tegowski Matthew , Fan Cheng , Baldwin Albert S. 
Published: December 2019

AbstractSeveral recent publications demonstrated that DRD2-targeting antipsychotics such as thioridazine induce proliferation arrest and apoptosis in diverse cancer cell types including those derived from brain, lung, colon, and breast. While most studies show that 10–20 µM thioridazine leads to reduced proliferation or increased apoptosis, here we show that lower doses of thioridazine (1–2 µM) target the self-renewal of basal-like breast cancer cells, but not breast cancer cells of other subtypes. We also show that all breast cancer cell lines tested express DRD2 mRNA and protein, regardless of thioridazine sensitivity. Further, DRD2 stimulation with quinpirole, a DRD2 agonist, promotes self-renewal, even in cell lines in which thioridazine does not inhibit self-renewal. This suggests that DRD2 is capable of promoting self-renewal in these cell lines, but that it is not active. Further, we show that dopamine can be detected in human and mouse breast tumor samples. This observation suggests that dopamine receptors may be activated in breast cancers, and is the first time to our knowledge that dopamine has been directly detected in human breast tumors, which could inform future investigation into DRD2 as a therapeutic target for breast cancer.
The impact of systemic treatment on brain metastasis in patients with non-small-cell lung cancer: A retrospective nationwide population-based cohort study
Authors: Lee Jung Soo , Hong Ji Hyung , Sun Der Sheng , Won Hye Sung , Kim Yeo Hyung , Ahn Mi Sun , Kang Seok Yun , Lee Hyun Woo , Ko Yoon Ho 
Published: December 2019

AbstractTo compare the incidence of brain metastases of advanced non-small cell lung cancer (NSCLC) treated with systemic cytotoxic chemotherapy (CC) and targeted therapy (TT), we performed a large-scale, retrospective, nationwide, cohort study. The population data were extracted from the Health Insurance Review and Assessment Service of Korea database from January 1, 2011, to November 30, 2016. Of the 29,174 patients newly diagnosed with stage IIIB or IV NSCLC who received systemic treatment, we investigated the initial and subsequent incidence of brain metastases. Besides, among 22,458 patients without initial brain metastasis, the overall cumulative incidence of subsequent brain metastases was compared according to systemic treatment administered. In total, 1,126 (5.0%) patients subsequently developed brain metastasis. The overall cumulative incidence of brain metastasis was significantly higher in the TT group than in the CC group (1-year cumulative incidence: 8.7% vs. 3.8%; 3-year: 17.2% vs. 5.0%; P < 0.001). Younger age, female sex, and first-line TT were significant risk factors for subsequent brain metastasis. In conclusion, the overall cumulative incidence of brain metastasis was significantly higher in patients received TT as the first-line treatment than in those received CC.
Invasion intensity influences scale-dependent effects of an exotic species on native plant diversity
Authors: Valone Thomas J. , Weyers David P. 
Published: December 2019

AbstractInvasive plant species reduce the diversity of natives by altering habitats or disturbance regimes, but it is less clear whether they do so via competitive exclusion. Here, we show that invader abundance alters scale-dependent competitive effects of invasion on native plant richness. Large-seeded exotic annual Erodium cicutarium invaded a site that manipulated rodent granivores. The invader became dominant on all plots but attained its highest abundance on plots that removed rodents. Invasion reduced plant abundance but not evenness; site-wide richness did not change over time on control plots but declined significantly on rodent removal plots. Species-area relationships within plots changed differently with invasion intensity: slopes increased and y-intercepts decreased on control plots relative to rodent removal plots. Changes in species-area slopes and y-intercepts following invasion suggest that common rather than rare species were most strongly impacted at small spatial scales on control plots, while common and rare species were both negatively impacted at all spatial scales on rodent removal plots. Small-seeded species declined in abundance following invasion more so than large-seeded species, indicative of competitive interactions mediated by seed size. These results reveal variation in scale-dependent competitive effects of invasion on native richness associated with invasion intensity.
Evaluation of binding and inhibition mechanism of dietary phytochemicals with sphingosine kinase 1: Towards targeted anticancer therapy
Authors: Gupta Preeti , Mohammad Taj , Dahiya Rashmi , Roy Sonam , Noman Omar Mohammed Ali , Alajmi Mohamed F. , Hussain Afzal , Hassan Md. Imtaiyaz 
Published: December 2019

AbstractSphingosine kinase 1 (SphK1) has recently gained attention as a potential drug target for its association with cancer and other inflammatory diseases. Here, we have investigated the binding affinity of dietary phytochemicals viz., ursolic acid, capsaicin, DL-α tocopherol acetate, quercetin, vanillin, citral, limonin and simvastatin with the SphK1. Docking studies revealed that all these compounds bind to the SphK1 with varying affinities. Fluorescence binding and isothermal titration calorimetric measurements suggested that quercetin and capsaicin bind to SphK1 with an excellent affinity, and significantly inhibits its activity with an admirable IC50values. The binding mechanism of quercetin was assessed by docking and molecular dynamics simulation studies for 100 ns in detail. We found that quercetin acts as a lipid substrate competitive inhibitor, and it interacts with important residues of active-site pocket through hydrogen bonds and other non-covalent interactions. Quercetin forms a stable complex with SphK1 without inducing any significant conformational changes in the protein structure. In conclusion, we infer that quercetin and capsaicin provide a chemical scaffold to develop potent and selective inhibitors of SphK1 after required modifications for the clinical management of cancer.
Diel changes and diversity of pufM expression in freshwater communities of anoxygenic phototrophic bacteria
Authors: Fecskeová Lívia Kolesár , Piwosz Kasia , Hanusová Martina , Nedoma Jiří , Znachor Petr , Koblížek Michal 
Published: December 2019

AbstractThe anoxygenic phototrophic bacteria (APB) are an active component of aquatic microbial communities. While DNA-based studies have delivered a detailed picture of APB diversity, they cannot provide any information on the activity of individual species. Therefore, we focused on the expression of a photosynthetic gene by APB communities in two freshwater lakes (Cep lake and the Římov Reservoir) in the Czech Republic. First, we analyzed expression levels of pufM during the diel cycle using RT-qPCR. The transcription underwent a strong diel cycle and was inhibited during the day in both lakes. Then, we compared DNA- (total) and RNA-based (active) community composition by sequencing pufM amplicon libraries. We observed large differences in expression activity among different APB phylogroups. While the total APB community in the Římov Reservoir was dominated by Betaproteobacteria, Alphaproteobacteria prevailed in the active library. A different situation was encountered in the oligotrophic lake Cep where Betaproteobacteria (order Burkholderiales) dominated both the DNA and RNA libraries. Interestingly, in Cep lake we found smaller amounts of highly active uncultured phototrophic Chloroflexi, as well as phototrophic Gemmatimonadetes. Despite the large diversity of APB communities, light repression of pufM expression seems to be a common feature of all aerobic APB present in the studied lakes.
Optical coherence angiography for pre-treatment assessment and treatment monitoring following photodynamic therapy: a basal cell carcinoma patient study
Authors: Gubarkova E. V. , Feldchtein F. I. , Zagaynova E. V. , Gamayunov S. V. , Sirotkina M. A. , Sedova E. S. , Kuznetsov S. S. , Moiseev A. A. , Matveev L. A. , Zaitsev V. Y. , Karashtin D. A. , Gelikonov G. V. , Pires L. , Vitkin A. , Gladkova N. D. 
Published: December 2019

AbstractMicrovascular networks of human basal cell carcinomas (BCC) and surrounding skin were assessed with optical coherence angiography (OCA) in conjunction with photodynamic therapy (PDT). OCA images were collected and analyzed in 31 lesions pre-treatment, and immediately/24 hours/3–12 months post-treatment. Pre-treatment OCA enabled differentiation between prevalent subtypes of BCC (nodular and superficial) and nodular-with-necrotic-core BCC subtypes with a diagnostic accuracy of 78%; this can facilitate more accurate biopsy reducing sampling error and better therapy regimen selection. Post-treatment OCA images at 24 hours were 98% predictive of eventual outcome. Additional findings highlight the importance of pre-treatment necrotic core, vascular metrics associated with hypertrophic scar formation, and early microvascular changes necessary in both tumorous and peri-tumorous regions to ensure treatment success.
Visuomotor perturbation in a continuous circle tracing task: novel approach for quantifying motor adaptation
Authors: Cohen Erez James , Wei Kunlin , Minciacchi Diego 
Published: December 2019

AbstractThe study of motor adaptation certainly has advanced greatly through the years and helped to shed light on the mechanisms of motor learning. Most paradigms used to study adaptation employ a discrete approach, where people adapt in successive attempts. Continuous tasks on the other hand, while known to possess different characteristics than discrete ones, have received little attention regarding the study motor adaptation. In this paper, we test for adaptation using a continuous circle tracing task with a visuomotor gain perturbation. To examine the feasibility of this task, 45 normal subjects divided into 3 groups were tested for adaptation, aftereffects, and generalization. All subjects exhibited a gradual adaptation when faced with a perturbation as well as opposite aftereffects once the perturbation was removed. Aftereffects tended to persist unless veridical feedback was given. The task generalized well both in size and in space. We believe that this task, by being continuous, could allow for a thorough investigation of visuomotor adaptation to gain perturbations in particular, and perhaps be expanded to other types of adaptations as well, especially when used alongside discrete tasks.
Perceptual vision training in non-sport-specific context: effect on performance skills and cognition in young females
Authors: Formenti Damiano , Duca Marco , Trecroci Athos , Ansaldi Leslie , Bonfanti Luca , Alberti Giampietro , Iodice Pierpaolo 
Published: December 2019

AbstractAlthough an increasing interest in vision training for sport performance, whether it may have a transfer to sport-specific skills and whether such transfer could be mediated by cognition remain open issues. To enlighten this point, we tested the effect of 6-weeks sport vision training programmes (requiring generic or volleyball-specific motor actions) in non-sport-specific context compared to a third group performing traditional volleyball training in sport-specific context. Fifty-one female volleyball players were randomly assigned to one of three groups. Before and after training period subjects were tested on accuracy of volleyball-specific skills and cognitive performance (clinical reaction time, executive control, perceptual speed). Accuracy of volleyball-specific skills improved after traditional volleyball training with respect to the vision training groups. Conversely, vision training groups improved cognitive performance (clinical reaction time, executive control and perceptual speed), as compared to traditional volleyball training group. Our results have shown that vision training in non-sport-specific context (both generic or with specific motor actions) improved cognitive performance, but seems to be less effective for improving sport-specific skills. These evidences suggest that environment in which exercises were performed plays a key role to improve perception and action in sport-specific skills, supporting the ecological approach to sport learning.
Obesity is associated with shorter telomeres in 8 year-old children
Authors: Clemente Diana B. P. , Maitre Lea , Bustamante Mariona , Chatzi Leda , Roumeliotaki Theano , Fossati Serena , Grazuleviciene Regina , Gützkow Kristine B. , Lepeule Johanna , Martens Dries S. , McEachan Rosie R. C. , Meltzer Helle M. , Petraviciene Inga , Slama Rémy , Tamayo-Uria Ibon , Urquiza Jose , Vafeiadi Marina , Wright John , Nawrot Tim S , Vrijheid Martine 
Published: December 2019

AbstractTelomere length is considered a biomarker of biological aging. Shorter telomeres and obesity have both been associated with age-related diseases. To evaluate the association between various indices of obesity with leukocyte telomere length (LTL) in childhood, data from 1,396 mother-child pairs of the multi-centre European birth cohort study HELIX were used. Maternal pre-pregnancy body mass index (BMI) and 4 adiposity markers in children at age 8 (6–11) years were assessed: BMI, fat mass, waist circumference, and skinfold thickness. Relative LTL was obtained. Associations of LTL with each adiposity marker were calculated using linear mixed models with a random cohort effect. For each 1 kg/m² increment in maternal pre-pregnancy BMI, the child’s LTL was 0.23% shorter (95%CI: 0.01,0.46%). Each unit increase in child BMI z-score was associated with 1.21% (95%CI: 0.30,2.11%) shorter LTL. Inverse associations were observed between waist circumference and LTL (−0.96% per z-score unit; 95%CI: −2.06,0.16%), and skinfold thickness and LTL (−0.10% per z-score unit; 95%CI: −0.23,0.02%). In conclusion, this large multicentric study suggests that higher child adiposity indicators are associated with short telomeres in children, and that associations are stronger for child BMI than for maternal pre-pregnancy BMI.
Plasma Transthyretin as a Predictor of Amnestic Mild Cognitive Impairment Conversion to Dementia
Authors: Tien Yi-Ting , Lee Wei-Ju , Liao Yi-Chu , Wang Wen-Fu , Jhang Kai-Ming , Wang Shuu-Jiun , Fuh Jong-Ling 
Published: December 2019

AbstractAmnestic mild cognitive impairment (MCI) is a prodromal stage of dementia, with a higher incidence of these patients progressing to Alzheimer’s disease (AD) than normal aging people. A biomarker for the early detection and prediction for this progression is important. We recruited MCI subjects in three teaching hospitals and conducted longitudinal follow-up for 5 years at one-year intervals. Cognitively healthy controls were recruited for comparisom at baseline. Plasma transthyretin (TTR) levels were measured by ELISA. Survival analysis with time to AD conversion as an outcome variable was calculated with the multivariable Cox proportional hazards models using TTR as a continuous variable with adjustment for other covariates and bootstrapping resampling analysis. In total, 184 MCI subjects and 40 sex- and age-matched controls were recruited at baseline. At baseline, MCI patients had higher TTR levels compared with the control group. During the longitudinal follow-ups, 135 MCI patients (73.4%) completed follow-up at least once. The TTR level was an independent predictor for MCI conversion to AD when using TTR as a continuous variable (p = 0.023, 95% CI 1.001–1.007). In addition, in MCI converters, the TTR level at the point when they converted to AD was significantly lower than that at baseline (328.6 ± 66.5 vs. 381.9 ± 77.6 ug/ml, p < 0.001). Our study demonstrates the temporal relationship between the plasma TTR level and the conversion from MCI to AD.
Environmental influences on light response parameters of net carbon exchange in two rotation croplands on the North China Plain
Authors: Bao Xueyan , Li Zhigang , Xie Futi 
Published: December 2019

AbstractThe ecosystem light response parameters, i.e. apparent quantum yield (α), maximum rate of ecosystem gross photosynthesis (Amax), and daytime ecosystem respiration (Rd), are very important when estimating regional carbon budgets. But they are not well understood in double cropping systems. Here, continuous flux data were collected from two rotation croplands in Yucheng (YC) and in Luancheng (LC) to describe the among-year variations inα,Amax, andRd, and to investigate variation mechanism on an annual scale. The three parameters exhibited marked fluctuations during the observation years. The annualα,Amax, andRdranged from 0.0022–0.0059 mg CO2μmol photon−1, from 2.33–4.43 mg CO2m−2s−1, and from 0.19–0.47 mg CO2m−2s−1at YC, and from 0.0016–0.0021 mg CO2μmol photon−1, from 3.00–6.30 mg CO2m−2s−1, and from 0.06–0.19 mg CO2m−2s−1at LC, respectively. AnnualαandRddeclined significantly when vapor pressure deficit (VPD) exceeded 1.05 kPa and increased significantly when canopy conductance (gc) exceed 6.33 mm/s at YC, but changed slightly when VPD andgcexceeded 1.16 kPa and 7.77 mm/s at LC, respectively. The fact that the negative effects of VPD andgconαandRdat LC were not as significant as they were at YC may be attributed to different climate conditions and planting species. A negative relationship (R2 = 0.90 for YC and 0.89 for LC) existed between VPD andgc. Therefore, the VPD, through its negative effect ongc, inhibitedαandRdindirectly. Among-yearAmaxvariation was mainly influenced by the annual mean surface soil temperature (Ts) of non-growing season of wheat significantly (R2 = 0.59, P < 0.01). Therefore, in future climate change scenarios, these environmental effects need to be included in carbon cycle models so that the accuracy of the carbon budget estimation can be improved.
Short-term Reproducibility of Pulmonary Nodule and Mass Detection in Chest Radiographs: Comparison among Radiologists and Four Different Computer-Aided Detections with Convolutional Neural Net
Authors: Kim Young-Gon , Cho Yongwon , Wu Chen-Jiang , Park Sejin , Jung Kyu-Hwan , Seo Joon Beom , Lee Hyun Joo , Hwang Hye Jeon , Lee Sang Min , Kim Namkug 
Published: December 2019

AbstractTo investigate the reproducibility of computer-aided detection (CAD) for detection of pulmonary nodules and masses for consecutive chest radiographies (CXRs) of the same patient within a short-term period. A total of 944 CXRs (Chest PA) with nodules and masses, recorded between January 2010 and November 2016 at the Asan Medical Center, were obtained. In all, 1092 regions of interest for the nodules and mass were delineated using an in-house software. All CXRs were randomly split into 6:2:2 sets for training, development, and validation. Furthermore, paired follow-up CXRs (n = 121) acquired within one week in the validation set, in which expert thoracic radiologists confirmed no changes, were used to evaluate the reproducibility of CAD by two radiologists (R1 and R2). The reproducibility comparison of four different convolutional neural net algorithms and two chest radiologists (with 13- and 14-years’ experience) was conducted. Model performances were evaluated by figure-of-merit (FOM) analysis of the jackknife free-response receiver operating curve and reproducibility rates were evaluated in terms of percent positive agreement (PPA) and Chamberlain’s percent positive agreement (CPPA). Reproducibility analysis of the four CADs and R1 and R2 showed variations in the PPA and CPPA. Model performance of YOLO (You Only Look Once) v2 based eDenseYOLO showed a higher FOM (0.89; 0.85–0.93) than RetinaNet (0.89; 0.85–0.93) and atrous spatial pyramid pooling U-Net (0.85; 0.80–0.89). eDenseYOLO showed higher PPAs (97.87%) and CPPAs (95.80%) than Mask R-CNN, RetinaNet, ASSP U-Net, R1, and R2 (PPA: 96.52%, 94.23%, 95.04%, 96.55%, and 94.98%; CPPA: 93.18%, 89.09%, 90.57%, 93.33%, and 90.43%). There were moderate variations in the reproducibility of CAD with different algorithms, which likely indicates that measurement of reproducibility is necessary for evaluating CAD performance in actual clinical environments.
O-GlcNAc stimulation: A new metabolic approach to treat septic shock
Authors: Ferron Marine , Cadiet Julien , Persello Antoine , Prat Valentine , Denis Manon , Erraud Angélique , Aillerie Virginie , Mevel Mathieu , Bigot Edith , Chatham John C. , Gauthier Chantal , Rozec Bertrand , Lauzier Benjamin 
Published: December 2019

AbstractSeptic shock is a systemic inflammation associated with cell metabolism disorders and cardiovascular dysfunction. Increases in O-GlcNAcylation have shown beneficial cardiovascular effects in acute pathologies. We used two different rat models to evaluate the beneficial effects of O-GlcNAc stimulation at the early phase of septic shock. Rats received lipopolysaccharide (LPS) to induce endotoxemic shock or saline (control) and fluid resuscitation (R) with or without O-GlcNAc stimulation (NButGT–10 mg/kg) 1 hour after shock induction. For the second model, rats received cecal ligature and puncture (CLP) surgery and fluid therapy with or without NButGT. Cardiovascular function was evaluated and heart and blood samples were collected and analysed. NButGT treatment efficiently increased total O-GlcNAc without modification of HBP enzyme expression.Treatment improved circulating parameters and cardiovascular function in both models, and restored SERCA2a expression levels. NButGT treatment also reduced animal mortality. In this study, we demonstrate that in septic shock O-GlcNAc stimulation improves global animal and cardiovascular function outcomes associated with a restoration of SERCA2a levels. This pre-clinical study opens avenues for a potential therapy of early-stage septic shock.
Transcriptome analysis of human brain microvascular endothelial cells response to Neisseria meningitidis and its antigen MafA using RNA-seq
Authors: Káňová Evelína , Tkáčová Zuzana , Bhide Katarína , Kulkarni Amod , Jiménez-Munguía Irene , Mertinková Patrícia , Drážovská Monika , Tyagi Punit , Bhide Mangesh 
Published: December 2019

AbstractInteraction of Neisseria meningitidis (NM) with human brain microvascular endothelial cells (hBMECs) initiates of multiple cellular processes, which allow bacterial translocation across the blood-brain barrier (BBB). NM is equipped with several antigens, which interacts with the host cell receptors. Recently we have shown that adhesin MafA (UniProtKB-X5EG71), relatively less studied protein, is one of those surface exposed antigens that adhere to hBMECs. The present study was designed to comprehensively map the undergoing biological processes in hBMECs challenged with NM or MafA using RNA sequencing. 708 and 726 differentially expressed genes (DEGs) were identified in hBMECs exposed to NM and MafA, respectively. Gene ontology analysis of the DEGs revealed that several biological processes, which may alter the permeability of BBB, were activated. Comparative analysis of DEGs revealed that MafA, alike NM, might provoke TLR-dependent pathway and augment cytokine response. Moreover, both MafA and NM were able to induce genes involved in cell surface modifications, endocytosis, extracellular matrix remodulation and anoikis/apoptosis. In conclusion, this study for the first time describes effect of NM on the global gene expression in hBMECs using high-throughput RNA-seq. It also presents ability of MafA to induce gene expression, which might aid NM in breaching the BBB.