tbuckley/cabot-search huggingface dataset:
Effects of a Novel Nitroxyl Donor in Acute Heart Failure
Authors: G. Michael Felker, John J.V. McMurray, John G. Cleland, Christopher M. O’Connor, John R. Teerlink, Adriaan A. Voors, Jan Belohlavek, Michael Böhm, Maria Borentain, Hector Bueno, Robert T. Cole, Mary M. DeSouza, Justin A. Ezekowitz, Gerasimos Filippatos, Ninian N. Lang, Paul D. Kessler, Felipe A. Martinez, Alex Mebazaa, Marco Metra, Arend Mosterd, Peter S. Pang, Piotr Ponikowski, Naoki Sato, Dietmar Seiffert, June Ye
Journal: JACC Heart Failure (2020)

The primary objective was to identify well-tolerated doses of cimlanod in patients with acute heart failure (AHF). Secondary objectives were to identify signals of efficacy, including biomarkers, symptoms, and clinical events.Nitroxyl (HNO) donors have vasodilator, inotropic and lusitropic effects. Bristol-Myers Squibb-986231 (cimlanod) is an HNO donor being developed for acute heart failure (AHF).This was a phase IIb, double-blind, randomized, placebo-controlled trial of 48-h treatment with cimlanod compared with placebo in patients with left ventricular ejection fraction ≤40% hospitalized for AHF. In part I, patients were randomized in a 1:1 ratio to escalating doses of cimlanod or matching placebo. In part II, patients were randomized in a 1:1:1 ratio to either of the 2 highest tolerated doses of cimlanod from part I or placebo. The primary endpoint was the rate of clinically relevant hypotension (systolic blood pressure <90 mm Hg or patients became symptomatic).In part I (n = 100), clinically relevant hypotension was more common with cimlanod than placebo (20% vs. 8%; relative risk [RR]: 2.45; 95% confidence interval [CI]: 0.83 to 14.53). In part II (n = 222), the incidence of clinically relevant hypotension was 18% for placebo, 21% for cimlanod 6 μg/kg/min (RR: 1.15; 95% CI: 0.58 to 2.43), and 35% for cimlanod 12 μg/kg/min (RR: 1.9; 95% CI: 1.04 to 3.59). N-terminal pro-B-type natriuretic peptide and bilirubin decreased during infusion of cimlanod treatment compared with placebo, but these differences did not persist after treatment discontinuation.Cimlanod at a dose of 6 μg/kg/min was reasonably well-tolerated compared with placebo. Cimlanod reduced markers of congestion, but this did not persist beyond the treatment period. (Evaluate the Safety and Efficacy of 48-Hour Infusions of HNO (Nitroxyl) Donor in Hospitalized Patients With Heart Failure [STANDUP AHF]; NCT03016325).
Impact of Geographic Region on the COMMANDER-HF Trial
Authors: João Pedro Ferreira, John G.F. Cleland, Carolyn S.P. Lam, Dirk J. van Veldhuisen, William M. Byra, David A. La Police, Stefan D. Anker, Mandeep R. Mehra, Céline Leroy, Valerie Eschwege, Marie Toussaint-Hacquard, Patrick Rossignol, Barry Greenberg, Faiez Zannad
Journal: JACC Heart Failure (2021)
Echocardiographic Monitoring Throughout Exercise: Better Than the Post-Treadmill Approach?⁎⁎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: Luc A. Piérard
Journal: Journal of the American College of Cardiology (2007)
The pleiotropic role of transcription factor STAT3 in oncogenesis and its targeting through natural products for cancer prevention and therapy
Authors: Manoj Garg, Muthu K. Shanmugam, Vipul Bhardwaj, Akul Goel, Rajat Gupta, Arundhiti Sharma, Prakash Baligar, Alan Prem Kumar, Boon Cher Goh, Lingzhi Wang, Gautam Sethi
Journal: Medicinal Research Reviews (2020)

Abstract Signal transducer and activator of transcription 3 (STAT3) is one of the crucial transcription factors, responsible for regulating cellular proliferation, cellular differentiation, migration, programmed cell death, inflammatory response, angiogenesis, and immune activation. In this review, we have discussed the classical regulation of STAT3 via diverse growth factors, cytokines, G‐protein‐coupled receptors, as well as toll‐like receptors. We have also highlighted the potential role of noncoding RNAs in regulating STAT3 signaling. However, the deregulation of STAT3 signaling has been found to be associated with the initiation and progression of both solid and hematological malignancies. Additionally, hyperactivation of STAT3 signaling can maintain the cancer stem cell phenotype by modulating the tumor microenvironment, cellular metabolism, and immune responses to favor drug resistance and metastasis. Finally, we have also discussed several plausible ways to target oncogenic STAT3 signaling using various small molecules derived from natural products.
15146 Effect of concomitant common cardiovascular medications on efficacy of sonidegib 200 mg daily in patients with locally advanced basal cell carcinoma: Results of the 42-month randomized, double-blind BOLT study
Authors: John Lear, Reinhard Dummer ProfDrMed, Alexander Guminski, Nicholas A. Squittieri, Li Liu, Michael Migden
Journal: Journal of the American Academy of Dermatology (2020)
Clinical Assessment of 177Lu-DOTATATE Quantification by Comparison of SUV-Based Parameters Measured on Both Post-PRRT SPECT/CT and 68Ga-DOTATOC PET/CT in Patients With Neuroendocrine Tumors
Authors: Philippe Thuillier, Meriem Maajem, Ulrike Schick, Frédérique Blanc-Beguin, Simon Hennebicq, Jean-Philippe Metges, Pierre-Yves Salaun, Véronique Kerlan, David Bourhis, Ronan Abgral
Journal: Clinical Nuclear Medicine (2020)

Introduction The aim of this study was to study the feasibility of an SUV-based 177 Lu-DOTATATE SPECT/CT quantification and to assess the correlation of different parameters with the corresponding measured on 68 Ga-DOTATOC PET/CT in patients with well-differentiated gastroenteropancreatic neuroendocrine tumors (WD-GEP-NET) treated with peptide receptor radionuclide therapy. Patients and Methods Patients with WD-GEP-NET who benefited from a pretherapeutic 68 Ga-DOTATOC PET/CT and a 177 Lu-DOTATATE SPECT/CT after the cycle 1 of peptide receptor radionuclide therapy were prospectively included. SPECT/CT acquisitions were performed on a system calibrated with a conversion factor of 9.48 counts/MBq per second and were reconstructed with an iterative algorithm allowing quantification using the SPECTRA Quant software (MIM Software, Cleveland, OH). For each patient, different SUV parameters were recorded on both PET/CT (Ga parameters) and SPECT/CT (Lu parameters) for comparison: physiological uptakes (liver/spleen), tumor uptake (1–10/patient; SUV max , SUV mean , SUV peak , MTV), tumor-to-liver and tumor-to-spleen ratios according to liver/spleen SUV max and SUV mean (TLR max , TLR mean , TSR max , and TSR mean , respectively). Results Ten patients (8 female; 2 male) aged from 50 to 83 years presenting with a metastatic progressive WD-GEP-NET (7 small intestine, 2 pancreas, 1 rectum) were included. Median values of lesional Lu-SUV were significantly lower than the corresponding Ga-SUV ( P &lt; 0.001), whereas median values of lesional Lu-MTV, Lu-TLR, and Lu-TSR were significantly higher than the corresponding Ga-MTV, Ga-TLR, and Ga-TSR ( P &lt; 0.02). Pearson correlation coefficients were strong for both SUV and MTV parameters (0.779–0.845), weak for TLR parameters (0.365–0.394), and moderate-to-strong for TSR parameters (0.676–0.750). Conclusions Our results suggest the feasibility of 177 Lu-DOTATATE SPECT/CT quantification in clinical practice and show a strong correlation of several SUV-based parameters with the corresponding in 68 Ga-DOTATOC PET/CT.
84MO A phase II, multicenter, open-label study of trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-expressing metastatic colorectal cancer (mCRC): DESTINY-CRC01
Authors: T. Yoshino, S. Siena, M. Di Bartolomeo, K. Raghav, T. Masuishi, F. Loupakis, H. Kawakami, K. Yamaguchi, T. Nishina, M. Fakih, E. Elez, J. Rodriguez, F. Ciardiello, K. Saxena, E. Yamamoto, K. Kobayashi, E. Bako, Y. Okuda, A. Grothey
Journal: Annals of Oncology (2020)
Lenalidomide, Pomalidomide and CC-220 Resistant Multiple Myeloma: Confirmation of Role of CRBN/IRF4 Axis and Identification of Multiple Disruption Mechanisms
Authors: Yuan Xiao Zhu, Chang-Xin Shi, Laura Ann Bruins, Xuewei Wang, Daniel Riggs, Brooke Porter, Jonathan Ahmann, Esteban Braggio, P. Leif Bergsagel, A. Keith Stewart
Journal: Blood (2017)
Genomic epidemiology of superspreading events in Austria reveals mutational dynamics and transmission properties of SARS-CoV-2
Authors: Alexandra Popa, Jakob-Wendelin Genger, Michael D. Nicholson, Thomas Penz, Daniela Schmid, Stephan W. Aberle, Benedikt Agerer, Alexander Lercher, Lukas Endler, Henrique Colaço, Mark Smyth, Michael Schuster, Miguel L. Grau, Francisco Martínez-Jiménez, Oriol Pich, Wegene Borena, Erich Pawelka, Zsofia Keszei, Martin Senekowitsch, Jan Laine, Judith H. Aberle, Monika Redlberger-Fritz, Mario Karolyi, Alexander Zoufaly, Sabine Maritschnik, Martin Borkovec, Peter Hufnagl, Manfred Nairz, Günter Weiss, Michael T. Wolfinger, Dorothee von Laer, Giulio Superti-Furga, Nuria Lopez-Bigas, Elisabeth Puchhammer-Stöckl, Franz Allerberger, Franziska Michor, Christoph Bock, Andreas Bergthaler
Journal: Science Translational Medicine (2020)

Superspreading events shaped the coronavirus disease 2019 (COVID-19) pandemic, and their rapid identification and containment are essential for disease control. Here, we provide a national-scale analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) superspreading during the first wave of infections in Austria, a country that played a major role in initial virus transmissions in Europe. Capitalizing on Austria's well-developed epidemiological surveillance system, we identified major SARS-CoV-2 clusters during the first wave of infections and performed deep whole-genome sequencing of more than 500 virus samples. Phylogenetic-epidemiological analysis enabled the reconstruction of superspreading events and charts a map of tourism-related viral spread originating from Austria in spring 2020. Moreover, we exploited epidemiologically well-defined clusters to quantify SARS-CoV-2 mutational dynamics, including the observation of low-frequency mutations that progressed to fixation within the infection chain. Time-resolved virus sequencing unveiled viral mutation dynamics within individuals with COVID-19, and epidemiologically validated infector-infectee pairs enabled us to determine an average transmission bottleneck size of 103 SARS-CoV-2 particles. In conclusion, this study illustrates the power of combining epidemiological analysis with deep viral genome sequencing to unravel the spread of SARS-CoV-2 and to gain fundamental insights into mutational dynamics and transmission properties.
16110 In silico analyses of the tumor microenvironment in basal cell carcinoma highlight the importance of TH2 cytokine profile, tumor-associated macrophages, and acquisition of mesenchymal stem cell-like phenotype in advanced and treatment-resistant tumors
Authors: Philippe Lefrançois, Pingxing Xie, Scott Gunn, None Jennifer, Amelia Martínez Villarreal, ‘Jennifer Gantchev, Denis Sasseville
Journal: Journal of the American Academy of Dermatology (2020)
Hypermetabolic Cerebral Metastases of Cardiac Myxoma on FDG PET/CT
Authors: Peipei Wang, Guozhu Hou, Fang Li, Xin Cheng
Journal: Clinical Nuclear Medicine (2020)

Abstract A 66-year-old woman with a history of surgical resection of left atrial myxoma 6 months ago presented with multiple brain lesions with MRI. An FDG PET/CT was performed for further evaluation. The images showed that cerebral tumors had variable and increased FDG uptake in general, and no other abnormal FDG-avid lesions were noted. The tumor of right occipital lobe was resected and confirmed as metastatic cardiac myxoma on histology.
417P Efficacy and safety of lorlatinib in subsequent lines of therapy in ALK and ROS1 positive lung cancer
Authors: A. Kumar, V. Noronha, V.M. Patil, A.S. Joshi, N.S. Menon, A. Kapoor, R. Kumar, A. Mahajan, A. Janu, O. Shetty, K. Prabhash
Journal: Annals of Oncology (2020)
Nanoparticle Vaccines Based on the Receptor Binding Domain (RBD) and Heptad Repeat (HR) of SARS-CoV-2 Elicit Robust Protective Immune Responses
Authors: Xiancai Ma, Fan Zou, Fei Yu, Rong Li, Yaochang Yuan, Yiwen Zhang, Xiantao Zhang, Jieyi Deng, Tao Chen, Zheng Song, Yidan Qiao, Yikang Zhan, Jun Liu, Junsong Zhang, Xu Zhang, Zhilin Peng, Yuzhuang Li, Yingtong Lin, Liting Liang, Guanwen Wang, Yingshi Chen, Qier Chen, Ting Pan, Xin He, Hui Zhang
Journal: Immunity (2020)
Push Button Population Health: The SMART/HL7 FHIR Bulk Data Access Application Programming Interface
Authors: Kenneth D. Mandl, Daniel Gottlieb, Joshua C. Mandel, Vladimir Ignatov, Raheel Sayeed, Grahame Grieve, James Jones, Alyssa Ellis, Adam Culbertson
Journal: npj Digital Medicine (2020)

Abstract The 21st Century Cures Act requires that certified health information technology have an application programming interface (API) giving access to all data elements of a patient’s electronic health record, “without special effort”. In the spring of 2020, the Office of the National Coordinator of Health Information Technology (ONC) published a rule—21st Century Cures Act Interoperability, Information Blocking, and the ONC Health IT Certification Program—regulating the API requirement along with protections against information blocking. The rule specifies the SMART/HL7 FHIR Bulk Data Access API, which enables access to patient-level data across a patient population, supporting myriad use cases across healthcare, research, and public health ecosystems. The API enables “push button population health” in that core data elements can readily and standardly be extracted from electronic health records, enabling local, regional, and national-scale data-driven innovation.
18F-Sodium Fluoride Positron Emission Tomography: An In Vivo Window Into Coronary Atherosclerotic Plaque Biology⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Richard T. George
Journal: Journal of the American College of Cardiology (2012)
Cyclophosphamide and Vinorelbine Activate Stem-Like CD8+ T Cells and Improve Anti-PD-1 Efficacy in Triple-Negative Breast Cancer
Authors: Paolo Falvo, Stefania Orecchioni, Roman Hillje, Alessandro Raveane, Patrizia Mancuso, Chiara Camisaschi, Lucilla Luzi, PierGiuseppe Pelicci, Francesco Bertolini
Journal: Cancer Research (2020)

Abstract Checkpoint inhibitors (CI) instigate anticancer immunity in many neoplastic diseases, albeit only in a fraction of patients. The clinical success of cyclophosphamide (C)-based haploidentical stem-cell transplants indicates that this drug may re-orchestrate the immune system. Using models of triple-negative breast cancer (TNBC) with different intratumoral immune contexture, we demonstrate that a combinatorial therapy of intermittent C, CI, and vinorelbine activates antigen-presenting cells (APC), and abrogates local and metastatic tumor growth by a T-cell–related effect. Single-cell transcriptome analysis of &amp;gt;50,000 intratumoral immune cells after therapy treatment showed a gene signature suggestive of a change resulting from exposure to a mitogen, ligand, or antigen for which it is specific, as well as APC-to-T-cell adhesion. This transcriptional program also increased intratumoral Tcf1+ stem-like CD8+ T cells and altered the balance between terminally and progenitor-exhausted T cells favoring the latter. Overall, our data support the clinical investigation of this therapy in TNBC. Significance: A combinatorial therapy in mouse models of breast cancer increases checkpoint inhibition by activating antigen-presenting cells, enhancing intratumoral Tcf1+ stem-like CD8+ T cells, and increasing progenitor exhausted CD8+ T cells.
GP is struck off for alleged sexual assault of which jury acquitted him
Authors: Clare Dyer
Journal: BMJ (2020)

A GP has been struck off the UK medical register for an alleged sexual assault of which a jury acquitted him1 after an appeal and five months in prison.

Olakunle Aronwojolu was sentenced to two years in prison in November 2014 after being convicted of sexually assaulting a receptionist in July 2013 at an Essex health centre where he worked as an out of hours GP.

He had led the younger woman to an examining room in the early hours of the morning after she had complained about her “flabby tummy,” ostensibly to teach her a sit-up technique. But in the examining room—which unlike the corridor was not covered by a camera—the receptionist said that he had inserted his hand in her underwear and rubbed her clitoris, continuing after she repeatedly …
Abstract 17095: Association of Cigarette and Electronic Cigarette Use Behaviors With Levels of Inflammatory and Oxidative Stress Biomarkers Among United States Adults, Path 2013-2014
Authors: Andrew Stokes, Anna E Wilson, Wubin Xie, Olusola A Orimoloye, Jessica L Fetterman, Andrew P Defilippis, Rachel J Keith, Emelia J Benjamin, Rose M Robertson, Aruni Bhatnagar, Naomi M Hamburg, Michael J Blaha
Journal: Circulation (2020)

Introduction: Electronic cigarette (e-cigarette) use has increased rapidly in recent years; however, the cardiovascular risks of e-cigarettes remain unclear. Using data from the Population Assessment of Tobacco and Health Survey, this study assesses the cross-sectional association of cigarette and e-cigarette use behaviors with markers of inflammation (high-sensitivity C-reactive protein [hsCRP], soluble intercellular adhesion molecule [sICAM], interleukin-6 [IL-6], fibrinogen), oxidative stress (8-isoprostane [F2PG2a]), and nicotine exposure (cotinine). Methods: We analyzed data from adults (18+ years) who provided urine and blood specimens at wave 1 (2013-2014). Biomarkers were examined as continuous and categorical variables using the clinical cut points of ≥3 mg/L for hsCRP &gt;10 ng/mL for cotinine, and the upper quartiles of fibrinogen (≥381mg/dL), IL-6 (≥2.32 pg/mL), sICAM (≥288.77 ng/mL), and 8-isoprostane (≥788 pg/mL). Progressively adjusted negative binomial and generalized structural equation models were used, as well as sensitivity checks to assess the robustness of associations. Results: Of the 7,019 participants (58.6% non-users, 1.8% current vapers, 29.7% current smokers, 9.9% dual users), 67.2% had ≥1 high inflammatory or oxidative stress marker. Current vapers had increased risk of high hsCRP (IRR 1.28; 95% CI,1.02-1.59) and sICAM (IRR 2.01; 95% CI,1.42-2.85) compared to non-users. Relative to current smokers, current vapers who were former smokers had lower risk of having ≥1 high inflammatory or oxidative stress marker (IRR 0.80; 95% CI,0.69-0.94). Dual users had higher levels of all 5 inflammatory and oxidative stress markers compared to never smokers in both continuous and categorical models, with similar levels compared to current smokers. Current smokers and dual users had higher levels of cotinine compared to exclusive vapers. Conclusions: This study suggests that current vapers may have lower levels of inflammatory and oxidative stress markers compared to current smokers, but only after complete cessation of combustible cigarettes. Our findings strengthen the need for longitudinal studies investigating the association of vaping with markers of cardiovascular risk, particularly among dual users.
163P Gastrointestinal stromal tumours (GIST) in adolescents and young adults (AYA) in an Asian institution from 2002 to 2018
Authors: E.Y.T. Wong, W.L. Goh, J. Hong, E.W.Y. Chang, V.S. Yang, J.Y. Chan, N. Somasundaram, J. Chiang, M. Farid, E.Y.L. Poon
Journal: Annals of Oncology (2020)
18104 Global provider specialty trends for genital extramammary Paget disease: A systematic review
Authors: Supriya Rastogi, Lauren M. Sadowsky, Rebecca Thiede, Taylor R. Erickson, Tammy Hua, Cory Kosche, Akash Rastogi, Kevin R. Patel, Corinne Miller MLIS, Bethanee J. Schlosser
Journal: Journal of the American Academy of Dermatology (2020)
Abstract 12223: The Prognostic Impact of Geometric Types and Its Shift in Patients With Heart Failure With Preserved Ejection Fraction: Insight From the Pursuit-hfpef Registry
Authors: Hiroyoshi Yamamoto, Yasumura Yoshio, Takahisa Yamada, Masaaki Uematsu, Shunsuke Tamaki, Yoshiharu Higuchi, Nakagawa Yusuke, Fuji Hisakazu, Masami Nishino, Shungo Hikoso, Daisaku Nakatani, Yasushi Sakata
Journal: Circulation (2019)

Background: Heart failure with preserved ejection fraction (HFpEF) has commonly been diagnosed as hypertensive heart disease, with a cardiac phenotype characterized by an increase in wall thickness...
Vaccinating the UK against covid-19
Authors: Azeem Majeed, Mariam Molokhia
Journal: BMJ (2020)

Background: Heterodimer cooperation between ErbB receptors has limited clinical usefulness of receptor tyrosine kinase inhibitors (TKIs), erlotinib and gefitinib in the treatment of cancer. However, combination treatment of TKIs with γ-tocotrienol targets multiple ErbB receptors and significantly inhibit +SA murine mammary tumor cell growth. Materials and Methods: Cell proliferation was determined by tetrazolium (MTT) assay and immunofluorescent Ki-67 staining. Western blot analysis was used to determine treatment effects on epidermal growth factor (EGF)-dependent mitogenic signaling. Results: Combined treatment of 3 μM γ-tocotrienol with 0.25 μM erlotinib or 0.5 μM gefitinib significantly inhibited +SA cell growth and reduced cyclin D1 and phosphorylated (active) Pdk-1, Akt, Stat3 and Stat5 levels. Conclusion: Combined treatment of γ-tocotrienol with erlotinib or gefitinib prevents ErbB receptor heterodimer cooperation and inhibits EGF-dependent mitogenic signaling in +SA murine mammary tumor cells. These findings strongly suggest that combination treatment may significantly improve therapeutic responsiveness in breast cancer patients.