tbuckley/cabot-search huggingface dataset:
Abstract PR05: Loss of PRC2 or KMT2D-COMPASS generates two quasi-mesenchymal cell states with distinct metastatic abilities
Authors: Yun Zhang, Joana Liu Donaher, Sunny Das, Xin Li, Ferenc Reinhardt, Jordan A. Krall, Arthur W. Lambert, Prathapan Thiru, Heather R. Keys, Mehreen Khan, Matan Hofree, Molly M. Wilson, Ozlem Yedier-Bayram, Nathan A. Lack, Tamer T. Onder, Tugba Bagci-Onder, Michael Tyler, Itay Tirosh, Aviv Regev, Jacqueline Lees, Robert A. Weinberg
Journal: Cancer Research (2020)

Abstract The epithelial-mesenchymal transition (EMT) is a key cell-biological program enabling carcinoma cell phenotypic plasticity. Accumulating evidence suggests EMT programs do not operate as a stereotypical program that functions as a binary switch, shifting cells from an epithelial (E) to a mesenchymal (M) state. Instead, EMT programs generate cells that enter into a series of intermediate states arrayed along the E-M phenotypic spectrum. At present, we still lack a coherent understanding of how carcinoma cells control their entrance into and residence in these various intermediate states, and which EMT intermediate state(s) favour the metastatic process. Here we characterize a new level of regulation of EMT, consisting of two chromatin-modifying complexes, PRC2 and KMT2D-COMPASS, that function as critical regulators to maintain stable residence of both normal and neoplastic cells in an epithelial state via regulating the downstream response of EMT-inducing signals. Dysfunction of either of these two complexes causes cells that were previously stably ensconced in an epithelial state to lapse into two distinct quasi-mesenchymal cell states with strongly differing metastatic abilities. These observations uncover a novel mechanism that regulates E-M plasticity, specifies which intermediate EMT state a cell will reside in, and thereby determines the metastatic ability of carcinoma cells. Citation Format: Yun Zhang, Joana Liu Donaher, Sunny Das, Xin Li, Ferenc Reinhardt, Jordan A. Krall, Arthur W. Lambert, Prathapan Thiru, Heather R. Keys, Mehreen Khan, Matan Hofree, Molly M. Wilson, Ozlem Yedier-Bayram, Nathan A. Lack, Tamer T. Onder, Tugba Bagci-Onder, Michael Tyler, Itay Tirosh, Aviv Regev, Jacqueline Lees, Robert A. Weinberg. Loss of PRC2 or KMT2D-COMPASS generates two quasi-mesenchymal cell states with distinct metastatic abilities [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PR05.
Deep Drug Penetration of Nanodrug Aggregates at Tumor Tissues by Fast Extracellular Drug Release
Authors: Yongchao Yao, Xin Dai, Yifeng Tan, Ying Chen, Chunyan Liao, Tian Yang, Yun Chen, Yunlong Yu, Shiyong Zhang
Journal: Advanced Healthcare Materials (2020)

Abstract Herein, a new nanodrug of azobenzene‐functionalized interfacial cross‐linked reverse micelles (AICRM) with 5‐fluorouracil loading (5‐FU@AICRM) is reported. Upon irradiation with 530 nm light in water, the surface azobenzenes of the nanoparticles change from polar cis ‐conformation to nonpolar trans ‐conformation, resulting in the aggregation of 5‐FU@AICRM within minutes. Simultaneously, the conformation change unlocks hydrophilic 5‐FU with a strong water immigration propensity, allowing them to spray out from the AICRM quickly. This fast release ensures a thorough release of the drug, before the aggregates are internalized by adjacent cells, making it possible to achieve deep tissue penetration. A study of in vivo anticancer activity in A549 tumor‐bearing nude mice shows that the tumor inhibition rate (TIR) of 5‐FU@AICRM is up to ≈86.2%, 31.6% higher than that of group without green light irradiation and 20.7% higher than that of carmofur (CF, a hydrophobic analog of 5‐FU)‐loaded AICRM (CF@AICRM), in which CF is released slowly under light irradiation because of its hydrophobicity. Fast drug release upon nanodrug aggregation provides a good solution for balancing the contradiction of “aggregation and penetration” in tumor treatment with nanodrugs.
The hexosamine biosynthesis pathway is a targetable liability in KRAS/LKB1 mutant lung cancer
Authors: Jiyeon Kim, Hyun Min Lee, Feng Cai, Bookyung Ko, Chendong Yang, Elizabeth L. Lieu, Nefertiti Muhammad, Shawn Rhyne, Kailong Li, Mohamed Haloul, Wen Gu, Brandon Faubert, Akash K. Kaushik, Ling Cai, Sahba Kasiri, Ummay Marriam, Kien Nham, Luc Girard, Hui Wang, Xiankai Sun, James Kim, John D. Minna, Keziban Unsal-Kacmaz, Ralph J. DeBerardinis
Journal: Nature Metabolism (2020)
Dual Targeting of G9a and DNA Methyltransferase‐1 for the Treatment of Experimental Cholangiocarcinoma
Authors: Leticia Colyn, Marina Bárcena‐Varela, Gloria Álvarez‐Sola, M. Ujue Latasa, Iker Uriarte, Eva Santamaría, Jose M. Herranz, Alvaro Santos‐Laso, Maria Arechederra, Mikel Ruiz de Gauna, Patricia Aspichueta, Matteo Canale, Andrea Casadei‐Gardini, Maria Francesconi, Simone Carotti, Sergio Morini, Leonard J. Nelson, Maria J. Iraburu, Chaobo Chen, Bruno Sangro, Jose J.G. Marin, Maria L. Martinez‐Chantar, Jesus M. Banales, Robert Arnes‐Benito, Meritxell Huch, John M. Patino, Altaf A. Dar, Mehdi Nosrati, Julen Oyarzábal, Felipe Prósper, Jesus Urman, Francisco Javier Cubero, Christian Trautwein, Carmen Berasain, Maite G. Fernandez‐Barrena, Matias A. Avila
Journal: Hepatology (2020)

Cholangiocarcinoma (CCA) is a devastating disease often detected at advanced stages when surgery cannot be performed. Conventional and targeted systemic therapies perform poorly, and therefore effective drugs are urgently needed. Different epigenetic modifications occur in CCA and contribute to malignancy. Targeting epigenetic mechanisms may thus open therapeutic opportunities. However, modifications such as DNA and histone methylation often coexist and cooperate in carcinogenesis. We tested the therapeutic efficacy and mechanism of action of a class of dual G9a histone-methyltransferase and DNA-methyltransferase 1 (DNMT1) inhibitors.Expression of G9a, DNMT1, and their molecular adaptor, ubiquitin-like with PHD and RING finger domains-1 (UHRF1), was determined in human CCA. We evaluated the effect of individual and combined pharmacological inhibition of G9a and DNMT1 on CCA cell growth. Our lead G9a/DNMT1 inhibitor, CM272, was tested in human CCA cells, patient-derived tumoroids and xenograft, and a mouse model of cholangiocarcinogenesis with hepatocellular deletion of c-Jun-N-terminal-kinase (Jnk)-1/2 and diethyl-nitrosamine (DEN) plus CCl4 treatment (JnkΔhepa + DEN + CCl4 mice). We found an increased and correlative expression of G9a, DNMT1, and UHRF1 in CCAs. Cotreatment with independent pharmacological inhibitors G9a and DNMT1 synergistically inhibited CCA cell growth. CM272 markedly reduced CCA cell proliferation and synergized with Cisplatin and the ERBB-targeted inhibitor, Lapatinib. CM272 inhibited CCA tumoroids and xenograft growth and significantly antagonized CCA progression in JnkΔhepa + DEN + CCl4 mice without apparent toxicity. Mechanistically, CM272 reprogrammed the tumoral metabolic transcriptome and phenotype toward a differentiated and quiescent status.Dual targeting of G9a and DNMT1 with epigenetic small molecule inhibitors such as CM272 is a potential strategy to treat CCA and/or enhance the efficacy of other systemic therapies.
SARS-CoV-2 mRNA Vaccines Foster Potent Antigen-Specific Germinal Center Responses Associated with Neutralizing Antibody Generation
Authors: Katlyn Lederer, Diana Castaño, Daniela Gómez Atria, Thomas H. Oguin, Sidney Wang, Tomaz B. Manzoni, Hiromi Muramatsu, Michael J. Hogan, Fatima Amanat, Patrick Cherubin, Kendall A. Lundgreen, Ying K. Tam, Steven H.Y. Fan, Laurence C. Eisenlohr, Ivan Maillard, Drew Weissman, Paul Bates, Florian Krammer, Gregory D. Sempowski, Norbert Pardi, Michela Locci
Journal: Immunity (2020)
16434 Health status, work productivity, and health care resource utilization in patients with moderate to severe atopic dermatitis: Analysis of the 2017 United States National Health and Wellness Survey
Authors: Shawn G. Kwatra, Amy H. Huang, Mamta Jhaveri, David Gruben, Selwyn Fung, Marco DiBonaventura
Journal: Journal of the American Academy of Dermatology (2020)
Coronary CT Angiography in Pediatric and Young Adult Coronary Allograft Vasculopathy
Authors: Vasu D. Gooty, Jeanne Dillenbeck, Yousef Arar, Daniel A. Castellanos, Gerald F. Greil, Nathanya B. Hernandez, Richard Kirk, Ryan Butts, Tarique Hussain
Journal: JACC. Cardiovascular imaging (2020)
A Closer Look on the Battlefield: The Salvaged Area at Risk as an Outcome Marker for Myocardial Reperfusion⁎⁎Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Authors: Matthias G. Friedrich
Journal: JACC. Cardiovascular imaging (2009)
Screening and diagnosis of tuberculosis in prisons in Russia and Eastern Europe: a cost-effectiveness analysis
Authors: Winetsky De, Negoescu Dm, Almukhamedova O, DeMarchis E, Dooronbekova A, Pulatov D, Vezhnina N, Zhussupov B, Douglas K. Owens, Jeremy Goldhaber-Fiebert
Journal: PLoS Medicine (2012)
Immune checkpoint-mediated psoriasis: A multicenter European study of 115 patients from the European Network for Cutaneous Adverse Event to Oncologic Drugs (ENCADO) group
Authors: Vasiliki Nikolaou, Vincent Sibaud, Davide Fattore, Pietro Sollena, Ariadna Ortiz-Brugués, Damien Giacchero, Maria Concetta Romano, Julia Riganti, Konstantinos Lallas, Ketty Peris, Dimitra Voudouri, Aimilios Lallas, Gabriella Fabbrocini, Elisabeth Lazaridou, Cristina Carrera, Maria Carmela Annunziata, Ernesto Rossi, Angela Patri, Dimitrios Rigopoulos, Alexander J. Stratigos, Zoe Apalla
Journal: Journal of the American Academy of Dermatology (2020)
Left Main Percutaneous Coronary Intervention Crossing the Threshold: Time for a Guidelines Revision!⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Jeffrey W. Moses, Martin B. Leon, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2009)
Reshaping preoperative treatment of pancreatic cancer in the era of precision medicine
Authors: R. Casolino, C. Braconi, G. Malleo, S. Paiella, C. Bassi, M. Milella, S.B. Dreyer, F.E.M. Froeling, D.K. Chang, A.V. Biankin, T. Golan
Journal: Annals of Oncology (2020)

•Molecular diversity of pancreatic cancer requires a paradigm shift towards a genomic-driven therapeutic approach.•Unselected treatment strategies demonstrate only limited efficacy in early-stage pancreatic cancer.•Personalised treatment in non-metastatic disease has potential to reduce pancreatic cancer mortality.•It is fundamental to implement preoperative clinical studies enriched for potential prognostic/predictive biomarkers.•Novel models of therapeutic development are warranted to accelerate progress in pancreatic cancer care and research. This review summarises the recent evidence on preoperative therapeutic strategies in pancreatic cancer and discusses the rationale for an imminent need for a personalised therapeutic approach in non-metastatic disease. The molecular diversity of pancreatic cancer and its influence on prognosis and treatment response, combined with the failure of 'all-comer' treatments to significantly impact on patient outcomes, requires a paradigm shift towards a genomic-driven approach. This is particularly important in the preoperative, potentially curable setting, where a personalised treatment allocation has the substantial potential to reduce pancreatic cancer mortality. This review summarises the recent evidence on preoperative therapeutic strategies in pancreatic cancer and discusses the rationale for an imminent need for a personalised therapeutic approach in non-metastatic disease. The molecular diversity of pancreatic cancer and its influence on prognosis and treatment response, combined with the failure of 'all-comer' treatments to significantly impact on patient outcomes, requires a paradigm shift towards a genomic-driven approach. This is particularly important in the preoperative, potentially curable setting, where a personalised treatment allocation has the substantial potential to reduce pancreatic cancer mortality.
The personal impact of covid-19 on trainees
Authors: Thomas R Fonseka, Ricky J Ellis
Journal: BMJ (2020)

Body art in the form of tattoos and piercing has become increasingly popular amongst children and teenagers, and is nowadays, more socially acceptable. This is despite media reports citing tissue destruction, and death. Our study explored the awareness and the experience of patients with congenital heart disease, as well as that of the cardiologists and professionals responsible for their care.
175P A study of neoadjuvant sintilimab combined with triplet chemotherapy of lipo-paclitaxel, cisplatin, and S-1 for resectable esophageal squamous cell carcinoma (ESCC)
Authors: Y. Gu, X. Chen, D. Wang, M. Ding, L. Xue, F. Zhen, J. Xu, M. Wang, Y. Li, N. Sun, C. Liu, L. Xu, Y. Wang, J. Luo
Journal: Annals of Oncology (2020)
Epidemiological serosurvey and molecular characterization of sexually transmitted infections among 1890 sheltered homeless people in Marseille: Cross-sectional one day-surveys (2000–2015)
Authors: Tran Duc Anh Ly, Van Thuan Hoang, Meriem Louni, Thi Loi Dao, Sekene Badiaga, Herve Tissot-Dupont, Philippe Brouqui, Philippe Colson, Philippe Gautret
Journal: Journal of Infection (2020)
Number of Social Determinants of Health and Fatal and Nonfatal Incident Coronary Heart Disease in the REGARDS Study
Authors: Monika M. Safford, Evgeniya Reshetnyak, Madeline R. Sterling, Joshua S. Richman, Paul M. Muntner, Raegan W. Durant, John Booth, Laura C. Pinheiro
Journal: Circulation (2020)

Social determinants of health (SDH) are individually associated with incident coronary heart disease (CHD) events. Indices reflecting social deprivation have been developed for population management, but are difficult to operationalize during clinical care. We examined whether a simple count of SDH is associated with fatal incident CHD and nonfatal myocardial infarction (MI).We used data from the prospective longitudinal REGARDS cohort study (Reasons for Geographic and Racial Differences in Stroke), a national population-based sample of community-dwelling Black and White adults age ≥45 years recruited from 2003 to 2007. Seven SDH from the 5 Healthy People 2020 domains included social context (Black race, social isolation); education (educational attainment); economic stability (annual household income); neighborhood (living in a zip code with high poverty); and health care (lacking health insurance, living in 1 of the 9 US states with the least public health infrastructure). Outcomes were expert adjudicated fatal incident CHD and nonfatal MI.Of 22 152 participants free of CHD at baseline, 58.8% were women and 42.0% were Black; 20.6% had no SDH, 30.6% had 1, 23.0% had 2, and 25.8% had ≥3. There were 463 fatal incident CHD events and 932 nonfatal MIs over a median of 10.7 years (interquartile range, 6.6 to 12.7). Fewer SDHs were associated with nonfatal MI than with fatal incident CHD. The age-adjusted incidence per 1000 person-years increased with the number of SDH for both fatal incident CHD (0 SDH, 1.30; 1 SDH, 1.44; 2 SDH, 2.05; ≥3 SDH, 2.86) and nonfatal MI (0 SDH, 3.91; 1 SDH, 4.33; ≥2 SDH, 5.44). Compared with those without SDH, crude and fully adjusted hazard ratios for fatal incident CHD among those with ≥3 SDH were 3.00 (95% CI, 2.17 to 4.15) and 1.67 (95% CI, 1.18 to 2.37), respectively; hazard ratios for nonfatal MI among those with ≥2 SDH were 1.57 (95% CI, 1.30 to 1.90) and 1.14 (95% CI, 0.93 to 1.41), respectively.A greater burden of SDH was associated with a graded increase in risk of incident CHD, with greater magnitude and independent associations for fatal incident CHD. Counting the number of SDHs may be a promising approach that could be incorporated into clinical care to identify individuals at high risk of CHD.
Abstract PO-001: xCT expression alters the epigenome and induces genomic instability
Authors: Dalton Hill, Jamshedur Rahman, Christien Kluwe, Pierre P. Massion
Journal: Cancer Research (2020)

Abstract Metabolic reprogramming, remodeling of the epigenetic landscape, and genomic instability are three processes that drive tumorigenesis. While each has been investigated individually, there is a growing interest in the interplay between each process during early cancer development. High expression of the cystine/glutamate antiporter SLC7A11 (xCT) is frequently seen in lung cancer. Our lab previously demonstrated overexpression of xCT in normal bronchial airway epithelial cells is sufficient to induce metabolic reprogramming. In this study, we investigated the effects of xCT overexpression in normal bronchial airway epithelial cells. We hypothesize that xCT overexpression both induces genomic instability and alters the epigenome in normal bronchial airway epithelial cells through the perturbation of intracellular metabolite levels. Through utilizing an alkaline comet assay, we discovered that xCT overexpression induces DNA damage, increasing the percentage of DNA in the comet tail by 15.1% (P=0.002). Furthermore, we found that xCT overexpression induces alterations to the histone modification landscape, most notably increasing H3K9me3 and H3K9ac by 3.2 and 3.9-fold (P=0.08) respectively. Finally, xCT overexpression shows higher tumorigenic potential through increased colony formation in a soft agar assay. Taken together, xCT overexpression in normal bronchial airway epithelial cells increases tumorigenic potential, induces metabolic reprogramming, causes higher levels of DNA damage, and alters the epigenetic landscape. Future experiments elucidating the links between these processes, including ChIP-seq and whole-genome bisulfite sequencing are currently underway. Establishing causal links between metabolic reprogramming, epigenetic alterations, and genomic instability are imperative in elucidating an effective, potentially multifaceted approach to treating early-stage lung cancer. Citation Format: Dalton Hill, Jamshedur Rahman, Christien Kluwe, Pierre P. Massion. xCT expression alters the epigenome and induces genomic instability [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PO-001.
15592 Psoriasis by body region: Does site predict recurrence?
Authors: Monica Rosales Santillan, Peyton Morss, Prerna Salian, Nicole Golbari, Martina Porter, Jerry Bagel, Alexa B. Kimball, Gilles J. Lauzon, P. Régine Mydlarski
Journal: Journal of the American Academy of Dermatology (2020)
Abstract 14783: Human Myocardium-on-a-Chip Enables Mechanistic Studies Into the Effects of Strain on Cardiac Fibrosis
Authors: Thomas C Bracco Gartner, Ye Wang, Jaap M den Toonder, Carlijn V Bouten, Joost P Sluijter, Willem J Suyker, Jesper Hjortnaes
Journal: Circulation (2019)

Introduction: In cardiac fibrosis, cardiac fibroblasts deposit excessive amounts of collagens in the extracellular matrix which cause arrhythmias and diastolic dysfunction. The biochemical stimuli ...
Thromboangiitis Obliterans (Buerger's Disease)
Authors: Jeffrey W. Olin
Journal: New England Journal of Medicine (2000)

Thromboangiitis obliterans (Buerger's disease) is a nonatherosclerotic segmental inflammatory disease that most commonly affects the small and medium-sized arteries, veins, and nerves of the arms and legs.1 Von Winiwarter first described a patient with thromboangiitis obliterans in 1879.2 Twenty-nine years later, Leo Buerger provided a detailed and accurate description of the pathological findings in 11 amputated limbs.3 Thromboangiitis obliterans differs from other forms of vasculitis in some important ways. Pathologically, there is a highly cellular and inflammatory thrombus with relative sparing of the blood-vessel wall. The acute-phase reactants (as assessed by the Westergren sedimentation rate and serum C-reactive protein level) . . .
Development of MOF “Armor‐Plated” Phycocyanin and Synergistic Inhibition of Cellular Respiration for Hypoxic Photodynamic Therapy in Patient‐Derived Xenograft Models
Authors: Danyang Chen, Meng Suo, Jiancheng Guo, Wenxue Tang, Wei Jiang, Ying Liu, Yanhong Duo
Journal: Advanced Healthcare Materials (2020)

Significant progress has been made in the use of phycocyanin (PC) as a photosensitizer (PS) agent for photodynamic therapy (PDT). The clinical use of PC, however, has been limited by its poor stability, unfavorable pharmacokinetics, limited tumor cell uptake, and the hypoxic nature of the tumor microenvironment. In this study, a novel biomimetic mineralization approach is described for encapsulating PC using zeolitic imidazolate framework-8 (ZIF-8), after which MPEG2000 -COOH is further utilized as an anchor on the ZIF/PC complex in order to yield MPEG2000 -ZIF/PC composites (PMs). These PMs are then used as a stable reinforced PS for PDT, effectively improving the intracellular delivery of this protein PS. In contrast to prior studies that have sought to overcome intratumoral hypoxia via increasing oxygen delivery to the tumor site, the mitochondrial complex I inhibitor papaverine (PPV) is instead utilized to reduce intratumor oxygen consumption in an effort to augment the PDT efficacy of the PMs. It is found that this combination treatment strategy markedly improves the antitumor properties of these PMs both in vitro and in patient-derived xenograft (PDX) models without inducing significant side effects. It is therefore proposed that the "armor-plating" of protein PS agents with ZIF-8 in combination with PPV may be a promising approach to precision medicine-mediated tumor treatment.
Racial and Ethnic Disparities in COVID-19–Related Infections, Hospitalizations, and Deaths
Authors: Katherine Mackey, Chelsea K. Ayers, Karli K. Kondo, Somnath Saha, Shailesh M. Advani, Sarah Young, Hunter Spencer, Max Rusek, Johanna Anderson, Stephanie Veazie, Mia Smith, Devan Kansagara
Journal: Annals of Internal Medicine (2020)

Data suggest that the effects of coronavirus disease 2019 (COVID-19) differ among U.S. racial/ethnic groups.
Distinct Diagnostic and Clinical Features of Bone Marrow Mastocytosis: A Study of the Registry of the European Competence Network on Mastocytosis (ECNM)
Authors: Massimiliano Bonifacio, Patrizia Bonadonna, Hanneke Oude Elberink, Björn van Anrooij, Aleksandra Górska, Magdalena Lange, Emir Hadzijusufovic, Luigi Scaffidi, Ilaria Tanasi, Cecelia Perkins, Virginia Valeria Ferretti, Anja Illerhaus, Thilo Jakob, Roberta Parente, Mohamad Jawhar, Francesca Caroppo, Alexander Zink, Alex Kilbertus, Akif Selim Yavuz, Michael Doubek, Hans Hagglund, Jens P. Panse, Vito Sabato, Elisabeth Aberer, Nadja Jaekel, Peter Vandenberghe, David Fuchs, Knut Brockow, Anna Belloni Fortina, Andreas Reiter, Massimo Triggiani, Khalid Shoumariyeh, Karin Hartmann, Chiara Elena, Olivier Hermine, Jason Gotlib, Marek Niedoszytko, Hanneke Kluin-Nelemans, Wolfgang R. Sperr, Peter Valent, Roberta Zanotti
Journal: Blood (2017)