tbuckley/cabot-search huggingface dataset:
TCT-812 Modified SCAI Classification for Cardiogenic Shock Is Associated With Increasing In-Hospital Mortality: A Report From the Cardiogenic Shock Working Group Registry
Authors: Katherine Thayer, Sarah Newman, Lija Swain, Arthur Garan, Jaime Hernandez-Montfort, Claudius Mahr, Mohyee Ayouty, Shashank Sinha, Esther Vorovich, Jacob Abraham, Navin Kapur
Journal: Journal of the American College of Cardiology (2019)
Significance of Recent Developments in Nuclear Cytology and Cytogenetics of the Mouse&lt;xref ref-type="fn" rid="fn1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: Elizabeth Fekete, Allen B. Griffen
Journal: JNCI Journal of the National Cancer Institute (1954)

Journal Article Significance of Recent Developments in Nuclear Cytology and Cytogenetics of the Mouse Get access Elizabeth Fekete, Elizabeth Fekete Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine Search for other works by this author on: Oxford Academic PubMed Google Scholar Allen B. Griffen Allen B. Griffen Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue 3, December 1954, Pages 801–811, https://doi.org/10.1093/jnci/15.3.801 Published: 01 December 1954
Divergent neuronal DNA methylation patterns across human cortical development reveal critical periods and a unique role of CpH methylation
Authors: Amanda J. Price, Leonardo Collado-Torres, Nikolay A. Ivanov, Wei Xia, Emily E. Burke, Joo Heon Shin, Ran Tao, Liang Ma, Yankai Jia, Thomas M. Hyde, Joel E. Kleinman, Daniel R. Weinberger, Andrew E. Jaffe
Journal: Genome biology (2019)

Abstract Background DNA methylation (DNAm) is a critical regulator of both development and cellular identity and shows unique patterns in neurons. To better characterize maturational changes in DNAm patterns in these cells, we profile the DNAm landscape at single-base resolution across the first two decades of human neocortical development in NeuN+ neurons using whole-genome bisulfite sequencing and compare them to non-neurons (primarily glia) and prenatal homogenate cortex. Results We show that DNAm changes more dramatically during the first 5 years of postnatal life than during the entire remaining period. We further refine global patterns of increasingly divergent neuronal CpG and CpH methylation (mCpG and mCpH) into six developmental trajectories and find that in contrast to genome-wide patterns, neighboring mCpG and mCpH levels within these regions are highly correlated. We integrate paired RNA-seq data and identify putative regulation of hundreds of transcripts and their splicing events exclusively by mCpH levels, independently from mCpG levels, across this period. We finally explore the relationship between DNAm patterns and development of brain-related phenotypes and find enriched heritability for many phenotypes within identified DNAm features. Conclusions By profiling DNAm changes in NeuN-sorted neurons over the span of human cortical development, we identify novel, dynamic regions of DNAm that would be masked in homogenate DNAm data; expand on the relationship between CpG methylation, CpH methylation, and gene expression; and find enrichment particularly for neuropsychiatric diseases in genomic regions with cell type-specific, developmentally dynamic DNAm patterns.
Clinical Outcomes in Early Breast Cancer With a High 21-Gene Recurrence Score of 26 to 100 Assigned to Adjuvant Chemotherapy Plus Endocrine Therapy
Authors: Joseph A. Sparano, Robert J. Gray, Della F. Makower, Kathy S. Albain, Thomas J. Saphner, Sunil S Badve, Lynne I. Wagner, Virginia G. Kaklamani, Maccon M. Keane, Henry L. Gomez, Pavan S. Reddy, Timothy F. Goggins, Ingrid A. Mayer, Deborah L. Toppmeyer, Adam M. Brufsky, Matthew P. Goetz, Jeffrey L. Berenberg, Catalin Mahalcioiu, Christine Desbiens, Daniel F. Hayes, Elizabeth C. Dees, Charles E. Geyer, John A. Olson, William C Wood, Tracy Lively, Soonmyung Paik, Matthew J. Ellis, Jeffrey Abrams, George W. Sledge
Journal: JAMA Oncology (2019)

A high 21-gene recurrence score (RS) by breast cancer assay is prognostic for distant recurrence of early breast cancer after local therapy and endocrine therapy alone, and for chemotherapy benefit.To describe clinical outcomes for women with a high RS who received adjuvant chemotherapy plus endocrine therapy in the TAILORx trial, a population expected to have a high distant recurrence rate with endocrine therapy alone.In this secondary analysis of data from a multicenter randomized clinical trial, 1389 women with hormone receptor-positive, ERBB2-negative, axillary node-negative breast cancer, and a high RS of 26 to 100 were prospectively assigned to receive adjuvant chemotherapy in addition to endocrine therapy. The analysis was conducted on May 12, 2019.The adjuvant chemotherapy regimen was selected by the treating physician.Freedom from recurrence of breast cancer at a distant site, and freedom from recurrence, second primary cancer, and death (also known as invasive disease-free survival [IDFS]).Among the 9719 eligible women, with a mean age of 56 years (range 23-75 years), 1389 (14%) had a recurrence score of 26 to 100, of whom 598 (42%) had an RS of 26 to 30 and 791 (58%) had an RS of 31 to 100. The most common chemotherapy regimens included docetaxel/cyclophosphamide in 589 (42%), an anthracycline without a taxane in 334 (24%), an anthracycline and taxane in 244 (18%), cyclophosphamide/methotrexate/5-fluorouracil in 52 (4%), other regimens in 81 (6%), and no chemotherapy in 89 (6%). At 5 years, the estimated rate of freedom from recurrence of breast cancer at a distant site was 93.0% (standard error [SE], 0.8%), freedom of recurrence of breast cancer at a distant and/or local regional site 91.0% (SE, 0.8%), IDFS 87.6% (SE, 1.0%), and overall survival 95.9% (SE, 0.6%).The estimated rate of freedom from recurrence of breast cancer at a distant site in women with an RS of 26 to 100 treated largely with taxane and/or anthracycline-containing adjuvant chemotherapy regimens plus endocrine therapy in the prospective TAILORx trial was 93% at 5 years, an outcome better than expected with endocrine therapy alone in this population.ClinicalTrials.gov identifier: NCT00310180.
TCT-359 Intravascular Coronary Plaque Characterization Using Hybrid Intravascular Ultrasound and Optical Coherence Tomography: A Preliminary Study Based on User Interpretation Compared With Histology Reference
Authors: Brian Li, Natasha Alves, Jill Weyers, Mark Harduar, Folake Kayode, Nicole Barritt, Brian Courtney
Journal: Journal of the American College of Cardiology (2019)
TCT-9 Quantitative Assessment of Lipid Composition by NIRS-IVUS Is Helpful for Differentiating Among Plaque Rupture, Plaque Erosion, and Calcified Nodule in the Culprit Lesion of ACS
Authors: Kosei Terada, Takashi Kubo, Yoshiki Matsuo, Yasushi Ino, Kunihiro Shimamura, Yasutsugu Shiono, Hiroki Emori, Yosuke Katayama, Atsushi Tanaka, Takeshi Hozumi, Takashi Akasaka
Journal: Journal of the American College of Cardiology (2019)
Low-Dose IFNγ Induces Tumor Cell Stemness in Tumor Microenvironment of Non–Small Cell Lung Cancer
Authors: Mengjia Song, Yu Ping, Kai Zhang, Li Yang, Feng Li, Chaoqi Zhang, Shaoyan Cheng, Dongli Yue, Nomathamsanqa Resegofetse Maimela, Jiao Qu, Shasha Liu, Ting Sun, Zihai Li, Jianchuan Xia, Bin Zhang, Liping Wang, Yi Zhang
Journal: Cancer Research (2019)

Abstract IFNγ is conventionally recognized as an inflammatory cytokine that plays a central role in antitumor immunity. Although it has been used clinically to treat a variety of malignancies, low levels of IFNγ in the tumor microenvironment (TME) increase the risk of tumor metastasis during immunotherapy. Accumulating evidence suggests that IFNγ can induce cancer progression, yet the mechanisms underlying the controversial role of IFNγ in tumor development remain unclear. Here, we reveal a dose-dependent effect of IFNγ in inducing tumor stemness to accelerate cancer progression in patients with a variety of cancer types. Low levels of IFNγ endowed cancer stem-like properties via the intercellular adhesion molecule-1 (ICAM1)–PI3K–Akt–Notch1 axis, whereas high levels of IFNγ activated the JAK1–STAT1–caspase pathway to induce apoptosis in non–small cell lung cancer (NSCLC). Inhibition of ICAM1 abrogated the stem-like properties of NSCLC cells induced by the low dose of IFNγ both in vitro and in vivo. This study unveils the role of low levels of IFNγ in conferring tumor stemness and elucidates the distinct signaling pathways activated by IFNγ in a dose-dependent manner, thus providing new insights into cancer treatment, particularly for patients with low expression of IFNγ in the TME. Significance: These findings reveal the dose-dependent effect of IFNγ in inducing tumor stemness and elucidate the distinct molecular mechanisms activated by IFNγ in a dose-dependent manner.
TCT-8 Updated 30-Day Outcomes for the U.S. Early Feasibility Study of the SAPIEN M3 Transcatheter Mitral Valve Replacement System
Authors: Raj Makkar, William O'Neill, Brian Whisenant, Mayra Guerrero, Ted Feldman, Chet Rihal, Jeremy Gorelick, John Webb
Journal: Journal of the American College of Cardiology (2019)
Long-Term Outcome of Treatment for Persistent Depressive Disorder: A Naturalistic Follow-Up Study
Authors: Jetske Emmelkamp, Lisa Kooistra, Patricia Van Oppen, Digna Van Schaik, Adriaan Hoogendoorn, Jack Dekker, Aartjan Beekman, James McCullough Jr., Jenneke Wiersma
Journal: Psychotherapy and Psychosomatics (2019)
Sputum microbiomic clustering in asthma and chronic obstructive pulmonary disease reveals a <i>Haemophilus</i>‐predominant subgroup
Authors: Sarah Diver, Matt Richardson, Koirobi Haldar, Michael A. Ghebre, Mohammadali Y. Ramsheh, Mona Bafadhel, Dhananjay Desai, Emma Suzanne Cohen, Paul Newbold, Laura Rapley, Paul Rugman, Ian D. Pavord, Richard D. May, Michael Barer, Christopher.E. Brightling
Journal: Allergy (2019)

Abstract Background Airway ecology is altered in asthma and chronic obstructive pulmonary disease (COPD). Anti‐microbial interventions might have benefit in subgroups of airway disease. Differences in sputum microbial profiles at acute exacerbation of airways disease are reflected by the γProteobacteria:Firmicutes (γP:F) ratio. We hypothesized that sputum microbiomic clusters exist in stable airways disease, which can be differentiated by the sputum γP:F ratio. Methods Sputum samples were collected from 63 subjects with severe asthma and 78 subjects with moderate‐to‐severe COPD in a prospective single centre trial. Microbial profiles were obtained through 16S rRNA gene sequencing. Topological data analysis was used to visualize the data set and cluster analysis performed at genus level. Clinical characteristics and sputum inflammatory mediators were compared across the clusters. Results Two ecological clusters were identified across the combined airways disease population. The smaller cluster was predominantly COPD and was characterized by dominance of Haemophilus at genus level (n = 20), high γP:F ratio, increased H influenzae , low diversity measures and increased pro‐inflammatory mediators when compared to the larger Haemophilus ‐low cluster (n = 121), in which Streptococcus demonstrated the highest relative abundance at the genus level. Similar clusters were identified within disease groups individually and the γP:F ratio consistently differentiated between clusters. Conclusion Cluster analysis by airway ecology of asthma and COPD in stable state identified two subgroups differentiated according to dominance of Haemophilus . The γP:F ratio was able to distinguish the Haemophilus ‐high versus Haemophilus ‐low subgroups, whether the Haemophilus‐ high group might benefit from treatment strategies to modulate the airway ecology warrants further investigation.
Isotretinoin is indirectly effective in sebocytes
Authors: D. Kovács, K. Hegyi, A. Szegedi, D. Deák, Sz. Póliska, R. Rühl, C.C. Zouboulis, D. Törőcsik
Journal: British Journal of Dermatology (2019)

In a recently published research letter, Burney et al. demonstrated that isotretinoin (13-cis-retinoic acid, 13CRA) induced acnegenic changes in cultured human SEB-1 sebocytes. 1However, Melnik et al. 2 suggested that the observed changes may largely be influenced by the Simian virus 40 (SV40) immortalization of the used cell line, which may inhibit the p53 pathway and, together with 13CRA, lead to changes such as downregulation of the forkhead box O (FOXO) pathway.In contrast, they found that the FOXO pathway was upregulated in samples from patients receiving 13CRA treatment for 6 weeks. 2 Importantly, the prominent differences, that 13CRA treatment arrests the cell cycle and induces apoptosis in SEB-1 sebocytes while in SZ95 sebocytes (a cell line also immortalized with the SV-40 large T antigen) 13CRA treatment does not affect programmed cell death, 3,4 suggest that SV-40 immortalization is not a fate-determining factor in these cell lines.Looking beyond these limitations, which arise from matching findings from a cell line with data from in vivo samples obtained at a given time point, the most challenging question regarding the effects of 13CRA is whether it is, indeed, the molecule responsible for the in vivo and in vitro observed changes.Besides having a weak binding affinity to its target receptors, RARs (retinoic acid receptors) and RXRs (retinoid X receptors), and a poor potential for direct transcriptional activation, 13CRA rapidly isomerizes to all-trans RA (ATRA) and 1052
TCT-400 Platelet Reactivity and Risk of Stent Thrombosis After Coronary Drug-Eluting Stent Implantation in Patients Treated With Oral Anticoagulation: The ADAPT-DES Study
Authors: Gennaro Giustino, Roxana Mehran, Ajay Jayant Kirtane, Paul Gurbel, Bernhard Witzenbichler, Franz-Josef Neumann, Giora Weisz, Akiko Maehara, Yiran Zhang, Michael Rinaldi, D. Christopher Metzger, Timothy Henry, David Cox, Peter L. Duffy, Ernest Mazzaferri, Bruce Brodie, Tom Stuckey, Gregg Stone
Journal: Journal of the American College of Cardiology (2019)
Is targeted lung cancer screening an opportune time to address cardiovascular risk?
Authors: Marie Fisk, Charlotte E Bolton
Journal: Thorax (2019)

<h3>Abstract</h3> Cell cycle dysregulation is prerequisite for cancer formation. However, it is unknown whether the mode of dysregulation affects disease characteristics. Here, we conduct comprehensive analyses of cell cycle checkpoint dysregulation events in breast cancer using patient data complemented by experimental investigations in multiple model systems: genetically-engineered mice, patient-derived xenografts, biomatrices, and cell lines. We find that <i>ATM</i> mutation predisposes the diagnosis of primary estrogen receptor (ER)+/human epidermal growth factor (HER)2- cancer in older women. Conversely, CHK2 dysregulation induces formation of metastatic, premenopausal ER+/HER2- breast cancer (p=0.001) that is treatment-resistant (HR=6.15, p=0.01). Lastly, while mutations in <i>ATR</i> alone are rare, <i>ATR/TP53</i> co-mutation is 12-fold enriched over expected in ER+/HER2- disease (p=0.002) and associates with metastatic progression (HR=2.01, p=0.006). Concordantly, ATR dysregulation induces metastatic phenotypes in <i>TP53</i> mutant, but not wild-type, cells. These results newly identify a role for distinct cell cycle dysregulation events in determining cancer subtype, metastatic potential, and treatment responsiveness. <h3>Statement of Significance</h3> These findings reframe the paradigm of cancer classification by demonstrating that cell cycle dysregulation decisions during malignant transformation can causally direct the type of cancer that evolves, its metastatic potential, and treatment responsiveness. These results provide rationale for delineating mode of checkpoint kinase dysregulation to improve diagnostic and therapeutic choices.
TCT-362 Comparison of Outcomes in Patients Undergoing Percutaneous Coronary Intervention Using Intravascular Ultrasound or Intravascular Optical Coherence Tomography
Authors: Fahed Darmoch, Yasser Al-Khadra, Homam Moussa Pacha, Mohamad Soud, M. Chadi Alraies
Journal: Journal of the American College of Cardiology (2019)
TCT-339 Partial Inferior Vena Cava Occlusion During Exercise in Heart Failure Patients Prevents Left Ventricular Pressure Overload, Improves Exercise Times, and Reduces Respiratory Rate: Mechanical “Balancing” of Biventricular Function as a Novel Therapy for Heart Failure Qualify of Life
Authors: Daniel Kaiser, Clayton Kaiser, James Canfield, Rupal Patel, Frederick St. Goar
Journal: Journal of the American College of Cardiology (2019)
TCT-689 Does Orienting Sapien 3 During Crimping in TAVR Affect Final Orientation to Coronaries to Impact TAV-in-TAV and Coronary Reaccess? A Pilot Study
Authors: Gilbert Tang, Syed Zaid, Eisha Gupta, Hasan Ahmad, Asaad Khan, Joshua Goldberg, Cenap Undemir, Nish Patel, Muhammad Khan, Steven Lansman, Jason Kovacic, George Dangas, Samin Sharma, Annapoorna Kini
Journal: Journal of the American College of Cardiology (2019)
Co-occurring Alterations in the RAS–MAPK Pathway Limit Response to MET Inhibitor Treatment in MET Exon 14 Skipping Mutation-Positive Lung Cancer
Authors: Julia K. Rotow, Philippe Gui, Wei Wu, Victoria M. Raymond, Richard B. Lanman, Frederic J. Kaye, Nir Peled, Ferran Fece de la Cruz, Brandon Nadres, Ryan B. Corcoran, Iwei Yeh, Boris C. Bastian, Petr Starostik, Kimberly Newsom, Victor R. Olivas, Alexander M. Wolff, James S. Fraser, Eric A. Collisson, Caroline E. McCoach, D. Ross Camidge, Jose Pacheco, Lyudmila Bazhenova, Tianhong Li, Trever G. Bivona, Collin M. Blakely
Journal: Clinical Cancer Research (2019)

Although patients with advanced-stage non-small cell lung cancers (NSCLC) harboring MET exon 14 skipping mutations (METex14) often benefit from MET tyrosine kinase inhibitor (TKI) treatment, clinical benefit is limited by primary and acquired drug resistance. The molecular basis for this resistance remains incompletely understood.Targeted sequencing analysis was performed on cell-free circulating tumor DNA obtained from 289 patients with advanced-stage METex14-mutated NSCLC.Prominent co-occurring RAS-MAPK pathway gene alterations (e.g., in KRAS, NF1) were detected in NSCLCs with METex14 skipping alterations as compared with EGFR-mutated NSCLCs. There was an association between decreased MET TKI treatment response and RAS-MAPK pathway co-occurring alterations. In a preclinical model expressing a canonical METex14 mutation, KRAS overexpression or NF1 downregulation hyperactivated MAPK signaling to promote MET TKI resistance. This resistance was overcome by cotreatment with crizotinib and the MEK inhibitor trametinib.Our study provides a genomic landscape of co-occurring alterations in advanced-stage METex14-mutated NSCLC and suggests a potential combination therapy strategy targeting MAPK pathway signaling to enhance clinical outcomes.
TCT-148 Does Energy Loss Index Improve the Comparison of Echocardiographic-Derived Aortic Valve Area Compared With Invasively–Derived Aortic Valve Area Pre-TAVR?
Authors: Rick Gaines, Ramy Mando, Craig Tucker, George Hanzel, Michael Gallagher, Francis Shannon, Amr Abbas
Journal: Journal of the American College of Cardiology (2019)
Qualitative Assessment of a State Partner–Facilitated Health Care–Associated Infection Prevention National Collaborative
Authors: Karen E. Fowler, Jane Forman, Jessica M. Ameling, Andrew J. Rolle, Deborah Bohr, Brittany Schwartz, Sue Collier, Vineet Chopra, Jennifer Meddings
Journal: Annals of Internal Medicine (2019)

Background: The Centers for Disease Control and Prevention (CDC) funded a 3-year national collaborative focused on facilitating relationships between health care–associated infection (HAI) prevention stakeholders within states and improving HAI prevention activities within hospitals. This program—STRIVE (States Targeting Reduction in Infections via Engagement)—targeted hospitals with elevated rates of common HAIs. Objective: To use qualitative methods to better understand STRIVE's effect on state partner relationships and HAI prevention efforts by hospitals. Design: Qualitative case study, by U.S. state. Setting: 7 of 22 eligible STRIVE state partnerships. Participants: Representatives from state hospital associations, state health departments, and other participating organizations (for example, Quality Innovation Networks–Quality Improvement Organizations), referred to as “state partners.” Measurements: Phone interviews (n = 17) with each organization were conducted, recorded, and transcribed. Results: State partners reported that relationships with each other and with participating hospitals improved through STRIVE participation. The partners saw improvements in hospital-level HAI prevention activities, such as improved auditing and feedback practices and inclusion of environmental services in prevention efforts; however, some noted those improvements may not be reflected in HAI rates. Many partners outlined plans to sustain their partner relationships by working on future state-level initiatives, such as opioid abuse prevention and antimicrobial stewardship. Limitation: Only 7 participating states were included; direct feedback from participating hospitals was not available. Conclusion: Although there were no substantial changes in aggregate HAI rates, STRIVE achieved its goal of improving state partner relationships and coordination. This improved collaboration may lead to a more streamlined response to future HAI outbreaks and public health emergencies. Primary Funding Source: Centers for Disease Control and Prevention.
A Genome-Wide, In Vivo, Dropout CRISPR Screen in Acute Myeloid Leukemia Identifies an Essential Role for Beta-Galactosylation in Leukemic Cell Homing
Authors: Francois Mercier, Jiantao Shi, David B Sykes, Elizabeth Miller, Toshihiko Oki, Cheuk-Him Man, Xiao-Jing Yan, Youmna Kfoury, Dongjun Lee, John G Doench, Franziska Michor, David T. Scadden
Journal: Blood (2017)
TCT-398 Impact of Long-Term Ticagrelor Monotherapy Following 1-Month Dual Antiplatelet Therapy in Patients Who Underwent Complex Percutaneous Coronary Intervention: Insights From the Global Leaders Trial
Authors: Patrick Serruys, Kuniaki Takahashi, Ply Chichareon, Norihiro Kogame, Mariusz Tomaniak, Rodrigo Modolo, Chun-Chin Chang, Hans-Peter Stoll, Christian Hamm, Philippe Gabriel Steg, Yoshinobu Onuma, Stephan Windecker, Marco Valgimigli
Journal: Journal of the American College of Cardiology (2019)
TCT-820 Systematical Review and Meta-Analysis on the Use of Inotropes and Vasopressors in Cardiogenic Shock: Time to Close the Gap Between Current Clinical Practice and Evidence?
Authors: Mina Karami, Veemal Hemradj, Dagmar Ouweneel, Alexander Vlaar, Wim K. Lagrand, Jose P.S. Henriques
Journal: Journal of the American College of Cardiology (2019)
Increased detection of enterovirus A71 infections, Germany, 2019
Authors: Sindy Böttcher, Sabine Diedrich, Kathrin Keeren
Journal: Eurosurveillance (2019)

We report on the increased circulation of enterovirus A71 in Germany in 2019. Strains were mainly identified in hospitalised patients with suspected aseptic meningitis/encephalitis. Molecular analysis showed co-circulation of EV-A71 sub-genogroups C1 and C4, a signal for physicians and public health authorities to include/intensify EV diagnostic in patients showing signs of aseptic meningitis, encephalitis or acute flaccid paralysis/myelitis.