tbuckley/cabot-search huggingface dataset:
Abstract 17251: Visualization of Neural Crest Cell Migration to the Dorsal Surface of Developing Zebrafish Myocardium
Authors: Varun Gudapati, Yichen Ding, Adam D Langenbacher, Chih-Chiang Chang, Jau-Nian Chen, Tzung K Hsiai
Journal: Circulation (2018)

Introduction: Neural crest (NC) cells are involved in cardiac development, and NC defects account for over 10% of all congenital heart disease. The migratory and morphogenic patterns of these NC cells are not well understood because conventional optical microscopes struggle to acquire images of live embryos with sufficient temporal and spatial resolution without causing major photo-damage. To address these issues, the lab has designed and built a light-sheet fluorescence microscope (LSFM) that is capable of acquiring dual-channel signals with high spatial and temporal resolution. Hypothesis: We hypothesize that the LSFM system will capture heart tube development at a cellular level and show the time point and location at which the NC cells integrate with the heart tube. Methods and Results: The transgenic line that is manipulated for this study is the Tg(neural crest:nfsB-mCherry, cardiac: eGFP) in which the heart tube fluoresces green while NC-derived cells fluoresce red. 10 zebrafish were imaged using the 3-D time-lapse LSFM setup from 15 hours post fertilization (hpf) to 36 hpf. The imaging data was qualitative and consistent across fish. Fig. 1 (a) shows mCherry NC-derived cells (red) integrating with eGFP cardiomyocytes (green) and areas of colocalization (yellow). Fig 1 (b) and (c) show the time course of the NC cell migration into the heart tube. By 26-27 hpf, the NC cells contacted the dorsal surface of the heart tube. By the 29 hpf, the NC-derived cells integrated into the heart tube and expressed nuclear eGFP, which is visualized by the yellow fluorescing portions of the image. Conclusions: We conclude that the LSFM was successful in acquiring distinct signals from the heart tube cells and the NC-derived cells. The temporal and spatial resolution was sufficient to observe NC migration at the single cell level and map out exactly where along the heart tubule the NC-cells entered.
Reply to Alexander Yang, Vincent L. Cannataro, Jeffrey P. Townsend’s Letter to the Editor, re: Ming-Jun Shi, Xiang-Yu Meng, Philippe Lamy, et al. APOBEC-mediated Mutagenesis as, a Likely Cause of FGFR3 S249C Mutation Over-representation in Bladder Cancer. Eur Urol 2019, 76:9–13
Authors: Ming-Jun Shi, Xiang-Yu Meng, Chun-Long Chen, Lars Dyrskjøt, François Radvanyi, Ludmila Prokunina-Olsson, Isabelle Bernard-Pierrot
Journal: European Urology (2019)
Urinary excretion of the carcinogenic heterocyclic amine 2-amino-9H-pyrido[2,3-b]indole (AαC) in smokers
Authors: Robert Turesky, Jian-Min Yuan, Renwei Wang, Sabrina Peterson, Mimi Yu
Journal: Cancer Research (2007)

831  Heterocyclic aromatic amines (HAAs) are a class of experimental animal carcinogens formed during the cooking of grilled meats, poultry, and fish. HAAs induce tumors in rodents at multiple sites that include: liver, stomach, colorectum, prostate and mammary gland. Some epidemiologic studies have reported elevated risks of cancer development in many of these organs of humans who frequently eat meat cooked well-done that can contain HAAs. These compounds have been implicated in the etiology of colorectal and other cancers in humans. Tobacco smoke is another potential source of exposure to HAAs. For example, 2-Amino-9H-pyrido[4,3-b]indole (AαC) occurs in tobacco smoke condensate at levels up to 260 ng/cigarette. These levels are 25 to 100-fold higher than the levels of benzo(a)pyrene and 4-aminobiphenyl, established human carcinogens measured in some brands of cigarettes. AαC is a potent liver carcinogen in mice and a potent colon-specific mutagen in transgenic mice. However, no data exist on in vivo exposure levels of AαC in humans or how they may vary by smoking status.  In this study, we assessed AαC levels in spot urine samples collected at baseline from 170 participants of the Shanghai Cohort Study, a population-based cohort study of diet and cancer among 18,244 men aged 45-64 years recruited during 1986-1989 in Shanghai, China. Subjects were interviewed in-person at baseline to obtain information on exposures, including cigarette smoking. We used a tandem, solvent-solid phase extraction method to isolate AαC in urine, followed by quantification using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) with a detection limit of 4 parts-per-trillion. Urine creatinine levels were determined using a standard method. As a means of adjusting for the varying concentration of spot urine samples across study subjects, we used the AαC/creatinine ratio as the biomarker for AαC exposure in vivo. The binomial test was used to compare the proportions of smokers versus nonsmokers who were positive for urinary AαC. The analysis of variance method was used to examine the association between levels of urinary AαC and number of cigarettes smoked per day.  Sixteen (18.6%) of 86 nonsmokers were positive for urinary AαC versus 41 (48.8%) of 84 cigarette smokers; the difference was statistically significant (p  This is the first report on the identification of AαC in urine of tobacco smokers. The potential role of this HAA in tobacco-related cancers in humans should be investigated.
Geographical variability, pheromones
Authors: Edward M. Miller
Journal: Behavioral and Brain Sciences (2000)

The worldwide variation in mating strategies can be explained by differential paternal investment theory, which traces the differences back to the climates where the various peoples (races) evolved. Male provisioning is necessary for women and children to survive cold winters, which is less essential for tropical women. Androstenone may be the substance that makes symmetrical men smell better to fertile females.
OS2.1 Incidence patterns for primary spinal cord ependymomas in adults: a Surveillance, Epidemiology, and End Results study
Authors: W Man, G Wang
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Ependymomas are the most common primary spinal cord tumors in adults. However, few population-based studies analyzed the epidemiological features for this tumor type. We explored Surveillance, Epidemiology, and End Results (SEER) database to evaluate the incidence patterns over time with regard to patient gender, race, age at diagnosis, and histological subtype for patients diagnosed with primary malignant spinal cord gliomas between 1973 and 2015. METHODS We queried SEER database to identify all adult patients (≥ 20 years of age) diagnosed with primary spinal cord ependymomas during 1973–2015. Variables of interest included gender, race, age at diagnosis, and histological subtype of tumor. The SEER*Stat 8.3.5 program was used to calculate frequencies, age-adjusted incidence rates (IR) with adjustment to the 2000 US Standard population and 95% confidence intervals (CI). An annual percentage change (APC) statistic with a 2-sided p-values was used to assess incidence patterns over time. RESULTS 1224 adult patients with primary spinal cord ependymomas were diagnosed between 1973 and 2015. Of the total population, 55.7% were males (n = 682) and 44.3% were females (n=542). Myxopapillary ependymomas (ICD-O-3 code 9394), papillary ependymomas (9393), ependymomas (9391) and anaplastic ependymomas (9392) accounts for 28.7% (n = 351), 0.5% (n = 6), 69.4% (n = 849) and 1.5% (n = 18) respectively. The overall age-adjusted IR for all adult primary spinal cord ependymomas was 0.16 per 100,000 (95%CI 0.15–0.17). The IR in male was higher than that in female (males 0.19 per 100,000 [95% CI 0.17–0.20], females 0.14 per 100,000 [95% CI 0.13–0.14]. Caucasians experienced higher IR (0.18 per 100,000 [95% CI 0.17–0.19]) compared to African Americans (0.19 per 100,000 [95% CI 0.07–0.12]) and the others (0.10 per 100,000 [95% CI 0.08–0.13]). Patients of age between 40 and 49 years experienced the highest IR (0.25 per 100,000 [95% CI 0.22–0.29]) than patients in the other age ranges. The most common histological subtypes were ependymomas (0.11 per 100,000 [95% CI 0.11–0.12]) and myxopapillary ependymomas (0.047 per 100,000 [95% CI 0.042–0.052]. The overall age-adjusted IR for all adult primary spinal cord ependymomas showed a statistically significant increase over time between 1973 and 2015 (APC=5.15, p&lt;0.01). The same increasing trend was found in Caucasians (APC=5.36, p&lt;0.01) and in both males (APC=5.13, p&lt;0.01) and females (APC=4.95, p&lt;0.01). CONCLUSION This study demonstrates an increasing IR of adult primary spinal cord ependymomas over the past four decades. Males, Caucasians and age between 40 and 49 years experienced a higher IR.
Abstract 1797: Characterization of a novel androgen receptor coregulator RIPK1
Authors: Cheng-Lung Hsu, Jai-Shin Liu, Ting-Wei Lin, Chun-Cheng Lin, Wen-Guey Wu
Journal: Cancer Research (2018)

Abstract Using bicalutamide-androgen receptor (AR) DNA binding domain-ligand binding domain as bait, we observed enrichment of FxxFY motif-containing peptides. Protein database searches revealed the presence of receptor-interacting protein kinase 1 (RIPK1) harboring one FxxFY motif. RIPK1 interacted directly with AR and suppressed AR transactivation in a dose-dependent manner. Domain mapping experiments showed that the FxxFY motif in RIPK1 is critical for interactions with AR and the death domain of RIPK1 plays a crucial role in its inhibitory effect on transactivation. In terms of tissue expression, RIPK1 levels were markedly higher in benign prostate hyperplasia and non-cancerous tissue regions relative to the tumor area. With the aid of computer modeling for screening of chemicals targeting activation function 2 (AF-2) of AR, we identified oxadiazole derivatives as good candidates and subsequently generated a small library of these compounds. A number of candidates could effectively suppress AR transactivation and AR-related functions in vitro and in vivo with tolerable toxicity via inhibiting AR-peptide, AR-coregulator and AR N-C interactions. Combination of these chemicals with antiandrogen had an additive suppressive effect on AR transcriptional activity. Our collective findings may pave the way in creating new strategies for the development and design of anti-AR drugs. Citation Format: Cheng-Lung Hsu, Jai-Shin Liu, Ting-Wei Lin, Chun-Cheng Lin, Wen-Guey Wu. Characterization of a novel androgen receptor coregulator RIPK1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1797.
P11.37 Evaluating water content and electrical properties at 200 kHz in brain and GBM tumor tissue of three TTFields patients with conventional imaging
Authors: Z Bomzon, C Wenger, H K Hershkovich, C Tempel Brami, M Giladi
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Electrical properties (EPs) of brain tissue, specifically brain tumors, crucially determine the field distribution of Tumor Treating Fields (TTFields), an anti-mitotic treatment approved for glioblastoma multiforme (GBM). Due to the correlation of TTFields efficacy and field intensity at the tumor region, the knowledge of EPs in each patient is of great importance for patient-specific planning of treatment. Water content electrical properties tomography (wEPT) is a non-invasive imaging technique using water content (WC) maps obtained from rapidly acquired and processed conventional sequences to estimate the EPs of brain tissue at 128 MHz. The WC maps of this approach are constructed from two spin echo sequences similar to a T1 and a PD image. Following previous studies in rat tumor models demonstrating promising wEPT mapping of EPs in the brain at 200, this study examines the feasibility of this approach in human GBM patients. MATERIAL AND METHODS For three patients of the EF-14 trial population, we divided T1 and PD images pixel-by-pixel to obtain the image ratio. Using a transfer function, WC maps were generated and maps of the electrical conductivity σ and the relative permittivity ε r at 200 kHz were calculated with two different equations. RESULTS The median value of estimated WC remains similar in healthy brain tissues among all patients, ~73.5% in the white matter, ~82% in the gray matter. The median values of wEPT-estimated σ at 200 kHz in the white matter is ~0.09 S/m and in the gray matter ~0.18 S/m, corresponding median values of ε r at 200 kHz are ~2100 and ~3000 in white and gray matter respectively. Contrary, in the tumor the spread between the median values of WC and EPs is much higher. Stating the most important findings, in the necrosis median WC are 90.3%, 92.3%, 85.2% in patients 1–3 respectively with corresponding median σ values of 0.494, 0.657, 0.25 S/m. In the enhancing tumor the spread of median WC is even higher (67.2%, 83.6%, 85.5%), yet lower spread but also very heterogeneous median σ values of 0.075 S/m, 0.208, 0.259 S/m are estimated with wEPT. CONCLUSION Our results demonstrate the adaption of wEPT for mapping of WC and EPs at 200 kHz in three human GBM patients. In contrast to the vastly irregular tumor tissue, our estimations in healthy brain tissue are similar between patients and in accordance with EPs experimentally measured during our animal experiments and consistent with reported values in the literature. Hence, wEPT is a promising, fast technique based on regular MRI that might help patient-specific treatment planning of TTFields therapy, although the mapping of tumor tissue needs further confirmation in a greater population and investigations of EPs of excised tumor tissue samples should be conducted.
Protective role of berberine on ulcerative colitis through modulating enteric glial cells–intestinal epithelial cells–immune cells interactions
Authors: Heng Li, Chen Fan, Huimin Lu, Chunlan Feng, Peilan He, Xiaoqian Yang, Caigui Xiang, Jianping Zuo, Wei Tang
Journal: Acta Pharmaceutica Sinica B (2019)

Ulcerative colitis (UC) manifests as an etiologically complicated and relapsing gastrointestinal disease. The enteric nervous system (ENS) plays a pivotal role in rectifying and orchestrating the inflammatory responses in gut tract. Berberine, an isoquinoline alkaloid, is known as its anti-inflammatory and therapeutic effects in experimental colitis. However, little research focused on its regulatory function on ENS. Therefore, we set out to explore the pathological role of neurogenic inflammation in UC and the modulating effects of berberine on neuro–immune interactions. Functional defects of enteric glial cells (EGCs), with decreased glial fibrillary acidic protein (GFAP) and increased substance P expression, were observed in DSS-induced murine UC. Administration of berberine can obviously ameliorate the disease severity and restore the mucosal barrier homeostasis of UC, closely accompanying by maintaining the residence of EGCs and attenuating inflammatory infiltrations and immune cells overactivation. In vitro, berberine showed direct protective effects on monoculture of EGCs, bone marrow-derived dendritic cells (BMDCs), T cells, and intestinal epithelial cells (IECs) in the simulated inflammatory conditions. Furthermore, berberine could modulate gut EGCs–IECs–immune cell interactions in the co-culture systems. In summary, our study indicated the EGCs–IECs–immune cell interactions might function as a crucial paradigm in mucosal inflammation and provided an infusive mechanism of berberine in regulating enteric neurogenic inflammation.
P14.100 Measurements of glioblastoma response to recurrence using spectroscopic measurements and MRI volumetry
Authors: J Chombar, A Heintz, J Constans
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Glioblastoma is the most aggressive and common primary malignant brain tumor in adults. The prognosis of patients with glioblastoma remains poor with a median life expectancy of 15 to 17 months and a survival rate of 5% at five years.Spectroscopy is becoming more and more used and the ratios studied allow in some cases a better prediction, at the recurrence, of the survival between certain ratios such as: Cho / Cr, NAA / Cr, Lac / Cr. Being able to combine all these ratios can allow us to obtain an additional survival index to take into account.This is why our study assesses whether MRS is coupled with volume, it is predictive of survival of the patient at 7 months. MATERIAL AND METHODS Population: 30 Patients with glioblastoma treated with the STUPP protocol with and without bevacizumab at recurrence over a period of 36 months. Patients divided into three different groups depending on the type of resection (subtotal (20), partial (13), and biopsy (7)).MRI sequences every 2 months on MRI 3T and 1.5T. Sequences we used: diffusion, T2, T2 *, FLAIR, 3D FLAIR, 3D T1 with gadolinium injection; also monovoxel spectroscopy (TE at 35 and 144 ms, sometimes 288 ms). The volume variations (calculated by Aw.Server and ITK) are evaluated according to the RANO criteria.The MRS ratios (calculated by jMRUI) were clinically used are Cho / Cr (tumor proliferation), NAA / Cr (infiltration) and Lac / Cr (glycolytic metabolism). Longitudinal analyzes of volumes and ratios. RESULTS 30 patients included in this study. The analysis of the results is that proliferation and / or glycolytic metabolism are more informative and predictive when there is absence of contrast enhancement, hyperperfusion or large volume variation. The global index (choline + lactate / NAA) could be a relevant criterion of judgment to better study the aggressiveness of the tumor and better predict the evolution of tumor volumes and survival. Intra-inter-operator differences on 2 segmentation software. CONCLUSION The study shows us and confirms that the widest possible resection is to favor. Spectroscopy ratios vary earlier than the volumetry and give more information on the tumor processes and is sometimes predictive of survival.
A Genotype-Guided Strategy for Oral P2Y<sub>12</sub> Inhibitors in Primary PCI
Authors: Daniel M.F. Claassens, Gerrit J.A. Vos, Thomas O. Bergmeijer, Renicus S. Hermanides, Arnoud W.J. van ’t Hof, Pim van der Harst, Emanuele Barbato, Carmine Morisco, Richard M. Tjon Joe Gin, Folkert W. Asselbergs, Arend Mosterd, Jean-Paul R. Herrman, Willem J.M. Dewilde, Paul W.A. Janssen, Johannes C. Kelder, Maarten J. Postma, Anthonius de Boer, Cornelis Boersma, Vera H.M. Deneer, Jurriën M. ten Berg
Journal: New England Journal of Medicine (2019)

It is unknown whether patients undergoing primary percutaneous coronary intervention (PCI) benefit from genotype-guided selection of oral P2Y12 inhibitors.
OS9.5 Evidence that adult glioblastoma adapts to standard therapy though chromatin remodeling
Authors: N Rippaus, J Manning, A Droop, M Al-Jabri, M Care, A F Bruns, M D Jenkinson, A Brodbelt, A Chakrabarty, A Ismail, S Short, L F Stead
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Glioblastoma (GBM) tumours recur following standard treatment in almost all cases. We use ‘omics technologies to simultaneously profile pairs of primary and matched recurrent GBM to specifically identify and characterise the cells that resisted treatment, with the aim of determining how to more effectively kill them. MATERIAL AND METHODS We have analysed high coverage RNAseq data from pairs of GBM tumours: primary de novo tumour and matched local recurrence from patients that underwent standard therapy. Our original cohort constituted 23 pairs and our validation cohort was an additional 22 pairs. We also cultured two plates of spheroids directly from a patient’s GBM, treating one with radiation and temozolomide. We monitored growth and captured and sequenced RNA from single cells at two time-points: one week post-treatment when the deviation between untreated and treated spheroid growth curves was most pronounced; and three weeks post-treatment when the growth rate of treated spheroids had recovered. We investigated differential gene expression between primary and recurrent pairs, and single cells pre- and post-treatment, and performed a bespoke per patient gene set enrichment analysis. RESULTS Differential gene expression analysis in 23 tumour pairs indicated a treatment-induced shift in cell states linked to normal neurogenesis and prompted us to develop a novel gene set enrichment analysis approach to identify gene regulatory factors that may orchestrate such a shift. This revealed the significant and universal dysregulation of genes, through therapy, that are targeted by a specific chromatin remodeling machinery. This finding was validated in an independent cohort of 22 further GBM pairs. To understand the therapeutic potential of this finding we must determine whether genes are dysregulated through therapy owing to a) their fixed expression in inherently treatment resistance cells in the primary tumour which get selected during therapy to increase the signal of that profile, or b) changes in expression during the process of cells acquiring treatment resistance. To inspect this, we analysed single cell gene expression data from GBM spheroids pre- and post-treatment. We found that there was significant dysregulation of the genes associated with the chromatin remodeling complex but only at the three-week post-treatment time-point. CONCLUSION Our results indicate that GBM cells are being transcriptionally reprogrammed in response to treatment; the mechanism of which may represent a therapeutic opportunity.
Correction to: Epigenetic signatures associated with imprinted paternally expressed genes in the Arabidopsis endosperm
Authors: Jordi Moreno-Romero, Gerardo Del Toro-De León, Vikash Kumar Yadav, Juan Santos-González, Claudia Köhler
Journal: Genome biology (2019)

Following publication of the original article [1], the authors reported that Additional file 4, "Table S5. Parent-of-origin RNAseq dataset of 4 DAP INTACT-purified endosperm of Col × Ler reciprocal crosses" had the following error: