tbuckley/cabot-search huggingface dataset:
The Transcription Factor ZEB2 Is Required to Maintain the Tissue-Specific Identities of Macrophages
Authors: Charlotte L. Scott, Wouter T’Jonck, Liesbet Martens, Helena Todorov, Dorine Sichien, Bieke Soen, Johnny Bonnardel, Sofie De Prijck, Niels Vandamme, Robrecht Cannoodt, Wouter Saelens, Bavo Vanneste, Wendy Toussaint, Pieter De Bleser, Nozomi Takahashi, Peter Vandenabeele, Sandrine Henri, Clare Pridans, David A. Hume, Bart N. Lambrecht, Patrick De Baetselier, Simon W.F. Milling, Jo A. Van Ginderachter, Bernard Malissen, Geert Berx, Alain Beschin, Yvan Saeys, Martin Guilliams
Journal: Immunity (2018)

Highlights•ZEB2 is highly expressed across the macrophage lineage•ZEB2 preserves the tissue-specific identities of macrophages across tissues•ZEB2 deficient macrophages are outcompeted by WT counterparts•LXRα is crucial for Kupffer cell identity and is maintained by ZEB2SummaryHeterogeneity between different macrophage populations has become a defining feature of this lineage. However, the conserved factors defining macrophages remain largely unknown. The transcription factor ZEB2 is best described for its role in epithelial to mesenchymal transition; however, its role within the immune system is only now being elucidated. We show here that Zeb2 expression is a conserved feature of macrophages. Using Clec4f-cre, Itgax-cre, and Fcgr1-cre mice to target five different macrophage populations, we found that loss of ZEB2 resulted in macrophage disappearance from the tissues, coupled with their subsequent replenishment from bone-marrow precursors in open niches. Mechanistically, we found that ZEB2 functioned to maintain the tissue-specific identities of macrophages. In Kupffer cells, ZEB2 achieved this by regulating expression of the transcription factor LXRα, removal of which recapitulated the loss of Kupffer cell identity and disappearance. Thus, ZEB2 expression is required in macrophages to preserve their tissue-specific identities.Graphical abstract
Abstract 2468: Increased expression of snoRNA in the tumor vasculature
Authors: Klarke M. Sample, Yingjie Nie, Roy Bicknell
Journal: Cancer Research (2018)

Abstract The tumor microenvironment has long been known to cause the differential expression of many genes within the endothelial cells that comprise the tumor vasculature. Yet, the differential expression of short nuclear RNA (snoRNA) has not previously been observed within tumor associated endothelial cells. A differential gene expression analysis was conducted on total RNAseq data derived from primary endothelial cell isolates and validated by qPCR. By these means, SNORD75, SNORD76, SCARNA7 and SNORA81 were demonstrated to be expressed at a higher level in liver, lung and colon associated tumor endothelial cells when compared to patient matched endothelial cells from healthy adjacent tissue. This data suggests that these four snoRNA molecules could be contributing to pathological angiogenesis and therefore tumor growth. Further work is currently being conducted to investigate this possibility. Citation Format: Klarke M. Sample, Yingjie Nie, Roy Bicknell. Increased expression of snoRNA in the tumor vasculature [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 2468.
Abstract 4116: Rapid imaging of tumor cell death in vivo using C2Am
Authors: Andre A. Neves, Kevin M. Brindle
Journal: Cancer Research (2018)

Abstract Cell death is an important target for imaging the early response of tumors to treatment. We describe here the validation of C2Am, a phosphatidylserine-binding agent based on the C2A domain of synaptotagmin-I, for detecting tumor cell death in vivo. Methods: The capability of (99m)Technetium-, (111)Indium-labelled or near- infrared fluorophore-labelled derivatives of C2Am for imaging tumor cell death was evaluated in implanted and genetically engineered [Fig.1] mouse models of lymphoma and in a human colorectal xenograft, using single photon CT (SPECT) and planar near-infrared fluorescence imaging, respectively [1,2]. Results: (99m)Tc-C2Am and (111)In-C2Am showed favorable biodistribution profiles, with predominantly renal clearance and low nonspecific retention in the spleen and liver at 24 h after probe administration. (99m)Tc-C2Am and (111In)-C2Am generated tumor-to-muscle ratios in drug-treated tumors of 4.3× and 2.2×, respectively, at 2 h and 7.3× and 4.1×, respectively, at 24 h after administration. A fluorophore-labelled C2Am derivative also showed predominantly renal clearance and high specificity and sensitivity for detecting low levels of tumor cell death (&amp;lt;5%). There was a significant correlation (R=0.9) between fluorescently labelled C2Am binding and histologic markers of cell death (cleaved caspase-3); no such correlation was observed with a site-directed mutant of C2Am that does not bind phosphatidylserine (iC2Am). Conclusions: Given the favorable biodistribution profile of radiolabelled C2Am derivatives, and their ability to produce rapid and cell death-specific image contrast, these agents have potential for clinical translation, particularly as PET tracers. We have initiated GMP manufacture and toxicology studies required for a Phase 1 trial. References: [1] Neves AA, Xie B, Fawcett S, Alam IS, Witney TH, de Backer MM, Summers J, Hughes W, McGuire S, Soloviev D, Miller J, Howat WJ, Hu DE, Rodrigues TB, Lewis DY, Brindle KM. Rapid Imaging of Tumor Cell Death In Vivo Using the C2A Domain of Synaptotagmin-I. (2017) J Nucl Med. 58:881-887. [2] Xie B, Tomaszewski MR, Neves AA, Ros S, Hu DE, McGuire S, Mullins SR, Tice D, Sainson RCA, Bohndiek SE, Wilkinson RW, Brindle KM. Optoacoustic Detection of Early Therapy-Induced Tumor Cell Death Using a Targeted Imaging Agent. (2017) Clin Cancer Res. 23:6893-6903. Citation Format: Andre A. Neves, Kevin M. Brindle. Rapid imaging of tumor cell death in vivo using C2Am [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 4116.
Roles of Cardiac Transcription Factors in Cardiac Hypertrophy
Authors: HiroshiAkazawa, IsseiKomuro
Journal: Circulation Research (2003)

Different cell types, equipped with unique structure and function, synthesize different sets of proteins on the basis of different patterns of gene expression, even though their genomes are identical. Cardiac transcription factors have been reported to control a cardiac gene program and thus to play a crucial role in transcriptional regulation during embryogenesis. Recently, postnatal roles of cardiac transcription factors have been extensively investigated. Consistent with the direct transactivation of numerous cardiac genes reactivated in response to hypertrophic stimulation, cardiac transcription factors are profoundly involved in the generation of cardiac hypertrophy or in cardioprotection from cytotoxic stress in the adult heart. In this review, the regulation of a cardiac gene program by cardiac transcription factors is summarized, with an emphasis on their potential role in the generation of cardiac hypertrophy.
Corticosteroids for Recurrent Pericarditis
Authors: MassimoImazio, AntonioBrucato, DavideCumetti, GiovanniBrambilla, BrunellaDemichelis, SilviaFerro, SilviaMaestroni, EnricoCecchi, RiccardoBelli, GiancarloPalmieri, RitaTrinchero
Journal: Circulation (2008)

Background— Corticosteroid use is widespread in recurrent pericarditis, even if rarely indicated, and high doses (eg, prednisone 1.0 to 1.5 mg · kg−1 · d−1) are generally recommended, although only weak evidence supports their use with possible severe side effects. The aim of this work was to compare side effects, recurrences and other complications, and hospitalizations of a low- versus high-dose regimen of prednisone for recurrent pericarditis. Methods and Results— A retrospective review of all cases of recurrent pericarditis treated with corticosteroids according to different regimens from January 1996 to June 2004 was performed in 2 Italian referral centers. One hundred patients with recurrent pericarditis (mean age, 50.1±15.8 years; 57 females) were included in the study; 49 patients (mean age, 47.5±16.0; 25 females) were treated with low doses of prednisone (0.2 to 0.5 mg · kg−1 · d−1), and 51 patients (mean age, 52.6±15.3; 32 females) were treated with prednisone 1.0 mg · kg−1 · d−1. Baseline demog...
Right Bundle-Branch Block and ST-Segment Elevation in Leads V1 Through V3
Authors: JosepBrugada, RamonBrugada, PedroBrugada
Journal: Circulation (1998)

Background—Five years ago, we described a specific ECG pattern of right bundle-branch block and ST-segment elevation in leads V1 through V3 associated with sudden death in patients without demonstrable structural heart disease. Information on long-term outcome has become available due to pooled data on a large cohort of patients with this syndrome who are followed at 33 centers worldwide. Methods and Results—Data on 63 patients (57 men; mean age, 38±17 years) with the described ECG pattern were analyzed in terms of arrhythmic events and sudden death. Events were analyzed for patients with at least one episode of aborted sudden death or syncope of unknown origin before recognition of the syndrome (symptomatic patients, n=41) and for patients in whom the ECG pattern was recognized by chance or because of screening related to sudden death of a relative (asymptomatic patients, n=22). During a mean follow-up of 34±32 months, an arrhythmic event occurred in 14 symptomatic patients (34%) and 6 asymptomatic patie...
BACH: Grand challenge on breast cancer histology images
Authors: Guilherme Aresta, Teresa Araújo, Scotty Kwok, Sai Saketh Chennamsetty, Mohammed Safwan, Varghese Alex, Bahram Marami, Marcel Prastawa, Monica Chan, Michael Donovan, Gerardo Fernandez, Jack Zeineh, Matthias Kohl, Christoph Walz, Florian Ludwig, Stefan Braunewell, Maximilian Baust, Quoc Dang Vu, Minh Nguyen Nhat To, Eal Kim, Jin Tae Kwak, Sameh Galal, Veronica Sanchez-Freire, Nadia Brancati, Maria Frucci, Daniel Riccio, Yaqi Wang, Lingling Sun, Kaiqiang Ma, Jiannan Fang, Ismael Kone, Lahsen Boulmane, Aurélio Campilho, Catarina Eloy, António Polónia, Paulo Aguiar
Journal: Medical Image Analysis (2019)

Breast cancer is the most common invasive cancer in women, affecting more than 10% of women worldwide. Microscopic analysis of a biopsy remains one of the most important methods to diagnose the type of breast cancer. This requires specialized analysis by pathologists, in a task that i) is highly time- and cost-consuming and ii) often leads to nonconsensual results. The relevance and potential of automatic classification algorithms using hematoxylin-eosin stained histopathological images has already been demonstrated, but the reported results are still sub-optimal for clinical use. With the goal of advancing the state-of-the-art in automatic classification, the Grand Challenge on BreAst Cancer Histology images (BACH) was organized in conjunction with the 15th International Conference on Image Analysis and Recognition (ICIAR 2018). BACH aimed at the classification and localization of clinically relevant histopathological classes in microscopy and whole-slide images from a large annotated dataset, specifically compiled and made publicly available for the challenge. Following a positive response from the scientific community, a total of 64 submissions, out of 677 registrations, effectively entered the competition. The submitted algorithms improved the state-of-the-art in automatic classification of breast cancer with microscopy images to an accuracy of 87%. Convolutional neuronal networks were the most successful methodology in the BACH challenge. Detailed analysis of the collective results allowed the identification of remaining challenges in the field and recommendations for future developments. The BACH dataset remains publicly available as to promote further improvements to the field of automatic classification in digital pathology.
High-Resolution Quantitative Computed Tomography Demonstrating Selective Enhancement of Medium-Size Collaterals by Placental Growth Factor-1 in the Mouse Ischemic Hindlimb
Authors: WeimingLi, WeiqunShen, RobertGill, AngelaCorbly, BonitaJones, RamaBelagaje, YukeZhang, ShaoqingTang, YanChen, YanZhai, GuomingWang, AsavariWagle, KwanHui, MichaelWestmore, JeffreyHanson, Yun-FeiChen, MichaelSimons, JaiPalSingh
Journal: Circulation (2006)

Background— The process of arteriogenesis after occlusion of a major artery is poorly understood. We have used high-resolution microcomputed tomography (μ-CT) imaging to define the arteriogenic response in the mouse model of hindlimb ischemia and to examine the effect of placental growth factor-1 (PlGF-1) on this process. Methods and Results— After common femoral artery ligation, μ-CT imaging demonstrated formation of collateral vessels originating near the ligation site in the upper limb and connecting to the ischemic calf muscle region. Three-dimensional μ-CT and quantitative image analysis revealed changes in the number of segments and the segmental volume of vessels, ranging from 8 to 160 μm in diameter. The medium-size vessels (48 to 160 μm) comprising 85% of the vascular volume were the major contributor (188%) to the change in vascular volume in response to ischemia. Intramuscular injections of Ad-PlGF-1 significantly increased Sca1+ cells in the circulation, α-actin–stained vessels, and perfusion ...
Abstract 1508: Cloning, expression and purification of <i>Cionasavignyi</i> polypeptide CS5931 and its antitumor activity
Authors: Yangyang Zhang, Honglin Lai, Weixiao An, Shousong Cao, Xiukun Lin
Journal: Cancer Research (2018)

Abstract Previous study in our laboratory has shown that a novel polypeptide CS5931 (molecular weight 5931 Da) derived from Ciona savignyi possesses potent cytotoxicity against a variety of human cancer cells including cervical carcinoma Hela cells, colorectal carcinoma HCT-116 and RKO cells, lung carcinoma A549 cells, and leukemia HL60 cells ,with IC50 values of 4.17, 2.50, 5.54, 4.69 and 4.98uM,respectively. This result suggested that HCT116 cells are the most sensitive to the treatment of CS5931. We also found that CS5931 markedly induced apoptosis in a dose-dependent manner in HCT116 cells by Annexin V-FITC/PI double staining analysis. However, its content in Ciona savignyi is very low thus developing a novel method for increase of the production of the polypeptide is promising. GRN polypeptides typically consist of 56-58 amino acids with six disulfide bonds and four beta-sheets to make the GRN polypeptide structurally compact and complex so large-scale preparation of natural polypeptide CS5931 is very difficult. Therefore, recombinant expression of CS5931 by genetic engineering is one of the effective ways to solve this problem. In the present study, we cloned a full length cDNA of CS5931 precursor by rapid amplification of cDNA ends (RACE) and obtained the amino acid sequence of CS5931. We further made the polypeptide expression with high efficiency in E. coli. The expressed protein was purified through affinity chromatography. The gene fragment coding CS5931 was successfully cloned and then linked into prokaryotic expression carrier pET28a(+) and pPICZαa, respectively. Two expression vectors pET28a(+)-CS5931 and pPICZαa-CS5931 were transformed into E. coli and Pichia pastoris, respectively. Then recombinant polypeptide CS5931 were successfully induced with high expression . To investigate the expression and anticancer effect of polypeptide CS5931 in different vectors and strains, we purified the expressed product developed suitable methods for CS5931 great expression while maintaining its potent anticancer activity and identified the role of CS5931 target proteins. Moreover, the purified polypeptide native CS5931 and recombinant CS5931 equally display great antitumor activity against HT29 cells. Our studies indicate that we have successfully cloned, expressed and purified Ciona savignyi polypeptide CS5931 and demonstrated its potent antitumor activity against colorectal cancer cells. Therefore, CS5931 may be developed as a novel anticancer agent in the treatment of colorectal cancer clinically. Citation Format: Yangyang Zhang, Honglin Lai, Weixiao An, Shousong Cao, Xiukun Lin. Cloning, expression and purification of Cionasavignyi polypeptide CS5931 and its antitumor activity [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 1508.
Abstract 5313: Occupational exposure to trichloroethylene and DNA methylation: a cross-sectional study
Authors: Jinming Zhang, Luoping Zhang, Roel Vermeulen, Wei Hu, Bryan A. Bassig, Jason Y. Wong, Min Shen, Bu-Tian Ji, Boris Reiss, Mark Purdue, Martyn T. Smith, Qing Lan, Nathaniel Rothman
Journal: Cancer Research (2018)

Abstract Trichloroethylene (TCE) is a chlorinated solvent that is often used in occupational settings for vapor degreasing of metal parts. In 2012, TCE was classified as a known human carcinogen (Group 1) by the International Agency for Research on Cancer, largely based on evidence for kidney cancer. Animal studies have suggested that TCE may modulate DNA methylation. We performed a cross-sectional study to examine the associations of DNA methylation of individual CpG sites with TCE exposure. We enrolled 80 workers from factories where TCE was used, as well as 96 unexposed controls from food and clothes manufacturing factories in the same region, and 69 exposed workers and 77 controls were available for analyses in this study. Personal exposure measurements (2-3 per subject) were collected for a full work shift using a 3MTM badge in both exposed workers and a subgroup of the control workers. Blood samples were collected from each subject and CpG methylation was assayed on the Illumina Infinium HumanMethylation450 BeadChip. After quality controls procedures, 485,512 CpG probes were available for analyses. We used separate multivariable linear regression models to examine the associations of TCE exposure and the methylation level at each single CpG site. All models were adjusted for age, sex, current smoking status, current alcohol consumption, recent infection, and body mass index. The median TCE exposure level in exposed subjects was 12 ppm (10th percentile: 2 ppm; 90th percentile: 45 ppm). We found 29 CpG probes that achieved genome-wide significance (p &amp;lt; 1.04x10-7) when comparing TCE exposed workers with controls. TCE exposure was associated with hypomethylation at nearly all (28/29) of those CpG probes. Of these 29 CpG probes, 6 CpGs showed a significant (p &amp;lt; 1.04x10-7) exposure-response relationship across the categories of controls and lower- (&amp;lt;12ppm) and higher-exposed (≥12 ppm) workers, and were mapped to 6 different chromosomes. To our knowledge, this is the first report that TCE exposure is associated with alterations in DNA methylation in a molecular epidemiologic study. Our findings may provide insight into potential biological mechanisms linking exposure to TCE and adverse health outcomes. Citation Format: Jinming Zhang, Luoping Zhang, Roel Vermeulen, Wei Hu, Bryan A. Bassig, Jason Y. Wong, Min Shen, Bu-Tian Ji, Boris Reiss, Mark Purdue, Martyn T. Smith, Qing Lan, Nathaniel Rothman. Occupational exposure to trichloroethylene and DNA methylation: a cross-sectional study [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 5313.
Mitochondrial Cardiomyopathy Evaluated With Cardiac Magnetic Resonance
Authors: MichioNakanishi, MasakiHarada, EijiTadamura, HirokazuKotani, RikaKawakami, KoichiroKuwahara, YasuakiNakagawa, SatoruUsami, HideyukiKinoshita, MasatakaFujiwara, KiminoriHosoda, KenjiUeshima, KazuwaNakao
Journal: Circulation (2007)
The Father of Spanish Dermatology
Authors: Tyler Marion, Kevin Cao, Jorge Roman
Journal: JAMA Dermatology (2018)

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Abstract 13175: Outcomes of Heart Failure (HF) Patients Admitted to the Intensive Care Unit (ICU): Impact of Early or Late ICU Admission
Authors: Douglas S Lee, Heather J Ross, Thomas H Stelfox, Robert A Fowler, Damon C Scales, Susanna Mak, Michael E Farkouh, Hannah Wunsch, Xuesong Wang, Jack V Tu, Therese A Stukel, Peter C Austin
Journal: Circulation (2016)

Background: Little is known about the outcomes of HF patients who are admitted to an ICU. We examined the outcomes of HF patients who were admitted to directly to the ICU (early) or admitted to the ICU after initial ward admission (late), compared to non-ICU admitted patients. Methods: We examined 118,595 HF patients (ICD-10 code I50) in Ontario, Canada, who were hospitalized from 2003-2012 using the Canadian Institute for Health Information Discharge Abstract Database. We examined the association of ICU admission and timing with: a) 30-day mortality using multiple Cox regression with time-varying covariates, and b) 30-day hospital readmissions using repeated events analysis approach of Prentice, Williams and Peterson. Results: Of the cohort, 24,119 (20%) were admitted to an ICU during the hospital stay, of whom 84% were admitted early (median age 76 years, 54% men) and 16% were admitted later (age 77 years, 53% men). 30-day mortality was higher in early and late ICU compared to no ICU: 13%, 27%, 10.5% (p &lt;.001). Multivariable-adjusted hazard ratios (HR) were: 1.65 (95%CI; 1.58-1.73) for early ICU (p&lt;.001) and 4.59 (95%CI; 4.31-4.89) for late ICU (p&lt;.001) vs. no ICU (referent). All-cause 30-day readmissions were also highest among late ICU, followed by early ICU, and lowest in non-ICU patients: 24.3, 22.9, 21.7 readmissions per 100 person-months (all p &lt;.001). Multivariable-adjusted repeated events analysis demonstrated a progressively increasing HRs for all-cause readmission: 1.07 (95%CI; 1.04-1.11) for early ICU (p&lt;.001) and 1.13 (95%CI; 1.04-1.22) for late ICU (p&lt;.01) vs. no ICU (referent). Median in-hospital costs were $16,553 for late ICU, $8587 for early ICU, and $7296 for non-ICU admitted patients (p &lt;.001). Conclusions: HF patients who are admitted to the ICU are sicker and experience increased risk of 30-day readmissions and death. Late ICU admissions were associated with the highest risk of death and readmission, and incurred substantially higher costs of care.