tbuckley/cabot-search huggingface dataset:
Abstract PO-015: Hypermethylated genes in leiomyosarcoma can be targeted through guadecitabine treatment
Authors: Nesrin Hasan, Cynthia De Carvalho Fischer, Anup Sharma, Nita Ahuja
Journal: Cancer Research (2020)

Abstract Leiomyosarcomas (LMS) are aggressive mesenchymal tumors of smooth muscle origin. Understanding the molecular alterations associated with LMS is needed to identify potential therapeutic targets. Epigenetic alterations such as hypermethylation of gene promoter regions with associated transcriptional silencing is a hallmark of most cancers. Epigenetic reprograming is fundamentally linked to tumor initiation, progression and metastasis. Frequent epigenetic alterations have been observed in LMS. Epigenetic drugs such as DNA methyltransferase inhibitors (DNMTi) have been used to reverse aberrant DNA methylation and restore expression of silenced genes. Our previous studies using DNMTi, including guadecitabine, have shown that DNMTi treatment has anti-proliferative and pro-apoptotic effects in in vitro and in vivo models of LMS. Our goal was to characterize the methylation changes following guadecitabine treatment of the leiomyosarcoma cell line SK-UT1. SK-UT1 cells were treated with guadecitabine (0.05 µM-0.1 µM) and methylation was determined using Illumina 450K platform. We filtered the promoter CpG island regions that respond to guadecitabine treatment and were associated with decreased methylation compared to untreated SK-UT1 control (p≤0.05, Δβ≥0.15). In order to assess the relevance of these differentially methylated regions, we compared them to the methylation and expression profiles of LMS patient samples (GSE68312). We focused on the genes that have decreased expression and are associated with increased methylation of the promoter CpG island regions in the patient LMS samples. In conclusion, treatment of SK-UT1 cell line with guadecitabine resulted in decrease of methylation of a subset of promoter CpG island regions that were differentially hypermethylated in LMS patient samples. Further studies are needed to explore the effect of differential methylation on gene expression in guadecitabine treated SK-UT1 cell line. Understanding the effect of DNMTi on LMS is needed to identify potential therapeutic applications targeting the epigenetic pathways. Funding supported by Astex Pharmaceuticals. Citation Format: Nesrin Hasan, Cynthia De Carvalho Fischer, Anup Sharma, Nita Ahuja. Hypermethylated genes in leiomyosarcoma can be targeted through guadecitabine treatment [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-015.
Unusual Pneumothorax with Cardiac Perforation by Bone Cement after Percutaneous Vertebroplasty
Authors: Soon Jin Kim, Kyung Hwa Kim
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

"Unusual Pneumothorax with Cardiac Perforation by Bone Cement after Percutaneous Vertebroplasty." American Journal of Respiratory and Critical Care Medicine, 203(8), pp. e29–e30
Kupffer cell release of platelet activating factor drives dose limiting toxicities of nucleic acid nanocarriers
Authors: Meredith A. Jackson, Shrusti S. Patel, Fang Yu, Matthew A. Cottam, Evan B. Glass, Ella N. Hoogenboezem, R. Brock Fletcher, Bryan R. Dollinger, Prarthana Patil, Danielle D. Liu, Isom B. Kelly, Sean K. Bedingfield, Allyson R. King, Rachel E. Miles, Alyssa M. Hasty, Todd D. Giorgio, Craig L. Duvall
Journal: Biomaterials (2020)
The value of subcutaneous vs. oral methotrexate: real‐world data from the German psoriasis registry PsoBest
Authors: K. Reich, C. Sorbe, L. Griese, J.L.K. Reich, M. Augustin
Journal: British Journal of Dermatology (2020)

Methotrexate (MTX) remains one of the most frequently used first-line systemic treatment options in patients with plaque-type psoriasis [1]. Direct head-to-head trials against adalimumab, infliximab and ixekizumab [2] as well as indirect comparisons [3] indicate lower efficacy compared to biologic therapies. The comparator studies were conducted with oral MTX which may be suboptimal compared to subcutaneous (SC) administration due to the generation of lower levels of biologically active MTX polyglutamate [4]. A clinical trial with SC MTX suggested improved long-term disease control compared to oral MTX in previous studies, but a direct head-to-head comparison was not performed [5, 6]. The route of administration did not influence response rates in a recent real-life study [7]. Here we report the effectiveness of oral versus subcutaneous MTX in the German psoriasis registry PsoBest.
Fast detection of SARS-CoV-2 RNA via the integration of plasmonic thermocycling and fluorescence detection in a portable device
Authors: Jiyong Cheong, Hojeong Yu, Chang Yeol Lee, Jung-uk Lee, Hyun-Jung Choi, Jae-Hyun Lee, Hakho Lee, Jinwoo Cheon
Journal: Nature Biomedical Engineering (2020)

The diagnosis of severe acute respiratory syndrome 2 (SARS-CoV-2) infection by quantitative PCR with reverse transcription (RT-qPCR) typically involves bulky instrumentation in centralized laboratories and an assay time of 1-2 h. Here, we show that SARS-CoV-2 RNA can be detected in 17 min via a portable device integrating reverse transcription, fast thermocycling (via plasmonic heating through magneto-plasmonic nanoparticles) and in situ fluorescence detection following magnetic clearance of the nanoparticles. The device correctly classified all nasopharyngeal, oropharyngeal and sputum samples from 75 patients with COVID-19 and 75 healthy controls, with good concordance in fluorescence intensity with standard RT-qPCR (Pearson coefficients > 0.7 for the N1, N2 and RPP30 genes). Fast, portable and automated nucleic acid detection should facilitate testing at the point of care.
Remdesivir: a pendulum in a pandemic
Authors: Ilan S Schwartz, Emily L Heil, Erin K McCreary
Journal: BMJ (2020)

Covid-19 has claimed over a million lives globally and devastated healthcare systems, economies, and societal welfare.Determining effective, safe, and scalable prevention and treatment measures is the top priority of the scientific community.Rapidly disseminating guidance as new data emerge regarding experimental therapies is also of utmost importance.The World Health Organisation (WHO) living guideline on drugs for covid-19 is updated in The BMJ in response to interim results from the SOLIDARITY trial for repurposed antiviral therapies. 1With this version of the guideline, the WHO and partners provide a weak recommendation against the use of remdesivir for patients with any severity of covid-19.This comes after the panel's previous weak recommendation for remdesivir in patients with severe covid-19, which had been made with caveats: that uncertain clinical benefits and cost-effectiveness of the agent may exacerbate existing health inequities, and that, given the uncertainty, active enrolment into ongoing randomised controlled trials should be continued.
13882 Trifarotene 50 μg/g cream: An effective and safe treatment for moderate facial and truncal acne
Authors: James del Rosso, Jerry Tan, Jonathan S. Weiss, Linda Stein Gold, Fran Cook-Bolden, Lawrence Eichenfield, Emil Tanghetti, Michael Graeber, Alessandra Alio Saenz, Faiz Ahmad
Journal: Journal of the American Academy of Dermatology (2020)
News FLASH-RT: To Treat GBM and Spare Cognition, Fraction Size and Total Dose Matter
Authors: Christina C. Huang, Marc S. Mendonca
Journal: Clinical Cancer Research (2020)

Data indicate that ultrahigh dose rate (>106 Gy/second) FLASH radiotherapy (FLASH-RT) delivery of radiation reduces normal tissue damage without compromising tumor response. Orthotopic glioblastoma mouse studies now demonstrate that radiation fraction size, total dose, and number of fractions are critical parameters for FLASH-RT cognitive sparing without compromising tumor response.See related article by Montay-Gruel et al., p. 775.
Pulmonary Hypertension: A Stage for Ventricular Interdependence?⁎⁎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: Henry H. Hsia, Francois Haddad
Journal: Journal of the American College of Cardiology (2012)
Pediatric In-Hospital Cardiac Arrest and Cardiopulmonary Resuscitation in the United States
Authors: Ryan W. Morgan, Matthew P. Kirschen, Todd J. Kilbaugh, Robert M. Sutton, Alexis A. Topjian
Journal: JAMA Pediatrics (2020)

Pediatric in-hospital cardiac arrest (IHCA) occurs frequently and is associated with high morbidity and mortality. The objective of this narrative review is to summarize the current knowledge and recommendations regarding pediatric IHCA and cardiopulmonary resuscitation (CPR).Each year, more than 15 000 children receive CPR for cardiac arrest during hospitalization in the United States. As many as 80% to 90% survive the event, but most patients do not survive to hospital discharge. Most IHCAs occur in intensive care units and other monitored settings and are associated with respiratory failure or shock. Bradycardia with poor perfusion is the initial rhythm in half of CPR events, and only about 10% of events have an initial shockable rhythm. Pre-cardiac arrest systems focus on identifying at-risk patients and ensuring that they are in monitored settings. Important components of CPR include high-quality chest compressions, timely defibrillation when indicated, appropriate ventilation and airway management, administration of epinephrine to increase coronary perfusion pressure, and treatment of the underlying cause of cardiac arrest. Extracorporeal CPR and measurement of physiological parameters are evolving areas in improving outcomes. Structured post-cardiac arrest care focused on targeted temperature management, optimization of hemodynamics, and careful intensive care unit management is associated with improved survival and neurological outcomes.Pediatric IHCA occurs frequently and has a high mortality rate. Early identification of risk, prevention, delivery of high-quality CPR, and post-cardiac arrest care can maximize the chances of achieving favorable outcomes. More research in this field is warranted.
Preneoplastic Alterations Define CLL DNA Methylome and Persist through Disease Progression and Therapy
Authors: Helene Kretzmer, Anat Biran, Noelia Purroy, Camilla K. Lemvigh, Kendell Clement, Michaela Gruber, Hongcang Gu, Laura Rassenti, Arman W. Mohammad, Connie Lesnick, Susan L. Slager, Esteban Braggio, Tait D. Shanafelt, Neil E. Kay, Stacey M. Fernandes, Jennifer R. Brown, Lili Wang, Shuqiang Li, Kenneth J. Livak, Donna S. Neuberg, Sven Klages, Bernd Timmermann, Thomas J. Kipps, Elias Campo, Andreas Gnirke, Catherine J. Wu, Alexander Meissner
Journal: Blood Cancer Discovery (2020)

Most human cancers converge to a deregulated methylome with reduced global levels and elevated methylation at select CpG islands. To investigate the emergence and dynamics of the cancer methylome, we characterized genome-wide DNA methylation in pre-neoplastic monoclonal B cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL), including serial samples collected across disease course. We detected the aberrant tumor-associated methylation landscape at CLL diagnosis and found no significantly differentially methylated regions in the high-count MBL-to-CLL transition. Patient methylomes showed remarkable stability with natural disease and post-therapy progression. Single CLL cells were consistently aberrantly methylated, indicating a homogeneous transition to the altered epigenetic state, and a distinct expression profile together with MBL cells compared to normal B cells. Our longitudinal analysis reveals the cancer methylome to emerge early, which may provide a platform for subsequent genetically-driven growth dynamics and together with its persistent presence suggests a central role in the normal-to-cancer transition.
The Calm Afterthe Storm: Long-Term Survival After Cardiogenic Shock⁎⁎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: Judith S. Hochman, Renato Apolito
Journal: Journal of the American College of Cardiology (2007)
RETRACTED: Acetylation of lactate dehydrogenase B drives NAFLD progression by impairing lactate clearance
Authors: Tongxin Wang, Kai Chen, Weilei Yao, Ruilong Zheng, Qiongyu He, Jun Xia, Juan Li, Yafei Shao, Li Zhang, Lu Huang, Longshan Qin, Mingming Xu, Zheng Zhang, Dingyu Pan, Zhen Li, Feiruo Huang
Journal: Journal of Hepatology (2020)
Abstract 2951: Estimation of Perfusion with <sup>13</sup> N-Ammonia Retention Underestimates the Frequency and Extent of Hibernating Myocardium when Compared to Quantification of Absolute Myocardial Blood Flow
Authors: Andrew J Luisi, Brendan M Heavey, John M Canty, Robert A deKemp, James A Fallavollita
Journal: Circulation (2007)

Background: Viable dysfunctional myocardium can be classified as chronically stunned (normal resting perfusion) or hibernating (reduced resting flow). While 13 N-ammonia (NH 3 ) retention (late uptake) is typically used to estimate perfusion, the frequency and extent of hibernating myocardium (HM) may differ when quantification of dynamically-acquired absolute myocardial blood flow (MBF) is performed. Methods: Patients with stable ischemic cardiomyopathy (n = 25, EF 32 ± 2%, NYHA Class 2.1 ± 0.7) who were candidates for an ICD for the primary prevention of sudden death underwent imaging with NH 3 and insulin-clamp 18 F-2-deoxyglucose (FDG). Segmental perfusion (17 segment LV model, % peak segment) was assessed by both retention (20 minute summed image) and absolute MBF using a 3-compartment model (ml/min/g). Normal segments were defined as perfusion ≤ 80% peak segment. Segments with &lt;50% peak segment FDG uptake were defined as scar. The remaining segments were considered HM if FDG/perfusion ratio was ≥ 1.2. Results: Of the 425 total segments, only 15 (3.5%) were considered HM when NH 3 retention was used to assess perfusion. In contrast, the number of HM segments increased markedly with quantification of absolute MBF (159 or 37%, p&lt;0.001 vs. retention), with a commensurate reduction in the number of normally-perfused segments. Conclusions: The estimation of perfusion with NH 3 retention significantly overestimates MBF (Figure ) and hence underestimates the frequency and extent of HM. While the differentiation of chronically stunned from HM may not influence the decision for revascularization, the distinction may be important if HM is an independent risk factor for sudden death.
Modulation of chronic airway inflammation in guinea pigs by oral tolerance:: evaluation of cellular infiltration and peribronchial edema
Authors: Viviane C. Ruiz, Tatiana Drewiacki, Edna A. Leick-Maldonado, Carla M. Prado, Adriane S. Nakashima, David I. Kasahara, Milton A. Martins, Iolanda F. L. C. Tibério
Journal: European Respiratory Journal (2003)
290MO Patient controlled analgesia (PCA) versus non-pca intravenous hydromorphone for severe cancer pain: Update from a multi-center, phase III randomized trial, HMORCT09-1
Authors: R. Lin, S. Lin, J. Zhu, S. Feng, Q. Wu, J. Fu, F. Wang, H. Li, X. Li, G. Zhang, Y. Yao, M. Xin, T. Lai, X. Lv, Y. Chen, Y. Lin, L. Hong, S. Lin, S. Zhao, C. Huang
Journal: Annals of Oncology (2020)
Dysregulated Glutamate Transporter SLC1A1 Propels Cystine Uptake via Xc− for Glutathione Synthesis in Lung Cancer
Authors: Wenzheng Guo, Kaimi Li, Beibei Sun, Dongliang Xu, Lingfeng Tong, Huijing Yin, Yueling Liao, Hongyong Song, Tong Wang, Bo Jing, Min Hu, Shuli Liu, Yanbin Kuang, Jing Ling, Qi Li, Yadi Wu, Qi Wang, Feng Yao, Binhua P. Zhou, Shu-Hai Lin, Jiong Deng
Journal: Cancer Research (2020)

Cancer cells need to generate large amounts of glutathione (GSH) to buffer oxidative stress during tumor development. A rate-limiting step for GSH biosynthesis is cystine uptake via a cystine/glutamate antiporter Xc-. Xc- is a sodium-independent antiporter passively driven by concentration gradients from extracellular cystine and intracellular glutamate across the cell membrane. Increased uptake of cystine via Xc- in cancer cells increases the level of extracellular glutamate, which would subsequently restrain cystine uptake via Xc-. Cancer cells must therefore evolve a mechanism to overcome this negative feedback regulation. In this study, we report that glutamate transporters, in particular SLC1A1, are tightly intertwined with cystine uptake and GSH biosynthesis in lung cancer cells. Dysregulated SLC1A1, a sodium-dependent glutamate carrier, actively recycled extracellular glutamate into cells, which enhanced the efficiency of cystine uptake via Xc- and GSH biosynthesis as measured by stable isotope-assisted metabolomics. Conversely, depletion of glutamate transporter SLC1A1 increased extracellular glutamate, which inhibited cystine uptake, blocked GSH synthesis, and induced oxidative stress-mediated cell death or growth inhibition. Moreover, glutamate transporters were frequently upregulated in tissue samples of patients with non-small cell lung cancer. Taken together, active uptake of glutamate via SLC1A1 propels cystine uptake via Xc- for GSH biosynthesis in lung tumorigenesis. SIGNIFICANCE: Cellular GSH in cancer cells is not only determined by upregulated Xc- but also by dysregulated glutamate transporters, which provide additional targets for therapeutic intervention.
Decidual-Like NK Cell Polarization: From Cancer Killing to Cancer Nurturing
Authors: Adriana Albini, Douglas M. Noonan
Journal: Cancer Discovery (2020)

Natural killer (NK) cells accumulate at the fetal-maternal interface and represent 70% of immune cells in the decidua (dNK) at first-trimester pregnancy; they are immune-tolerant toward the semiallogenic fetus and are "nurturing" and nonkilling NK cells. A subset of NK cells in patients with cancer have features in common with dNK, which include expressing CD56, CD9, CD49a, and CXCR3, being poorly cytotoxic and proangiogenic, and mimicking the decidual nurturing role. In the oncologic patient, several factors can "decidualize" NK cells, turning them into immune-suppressant, growth-promoting proangiogenic cells. Here, we suggest ways to sharpen their blunted blades and intercept and curb their cancer-nurturing attitudes to restore their cytotoxic capabilities.
Periodontal health and disease: The contribution of genetics
Authors: Luciana Macchion Shaddox, Lorri Ann Morford, Luigi Nibali
Journal: Periodontology 2000 (2020)

Abstract Periodontitis is an infectious, inflammatory disease that is associated with a complex interplay between specific bacteria, host response, and environmental factors. Because of its high degree of familial aggregation, specifically for the more aggressive forms of the disease, genetics factors have been implicated in disease pathogenesis for several decades. This review provides an overview of what we currently know regarding the genetic and epigenetic contributions to periodontal disease and discusses future opportunities in the field.
Abstract 19223: Injection of Nanoformulated CaCl2 into Intrinsic Cardiac Ganglionic Plexi Suppresses Ganglionic Nerve Activity and Postoperative Atrial Fibrillation
Authors: Michael P Oquinn, Kenneth J Dormer, Karoly Kaszala, Kenneth A Ellenbogen, Jose F Huizar, Alex Tan
Journal: Circulation (2017)

Background: Postoperative atrial fibrillation (POAF), a complication of cardiac surgery, causes significant morbidity. Sympathetic surge promotes remodeling, leading to POAF. Intracellular Ca++ ove...
231P Phase II study of pembrolizumab in docetaxel-pretreated patients with metastatic castration-resistant prostate cancer (mCRPC): Updated follow-up of cohorts (C) 1-3 from KEYNOTE-199
Authors: J.C.H. Goh, J.M. Piulats, M. Gross-Goupil, U.N. Vaishampayan, R. de Wit, T.V. Alanko, S. Fukasawa, K. Tabata, S. Feyerabend, R. Berger, H. Wu, J. Kim, C. Schloss, J.S. de Bono, E.S. Antonarakis
Journal: Annals of Oncology (2020)
Stress Myocardial Perfusion Imaging by Computed Tomography: A Dynamic Road Is Ahead⁎⁎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: Ron Blankstein, Michael Jerosch-Herold
Journal: JACC. Cardiovascular imaging (2010)
Treatment interventions to maintain abstinence from alcohol in primary care: systematic review and network meta-analysis
Authors: Hung-Yuan Cheng, Luke A McGuinness, Roy G Elbers, Georgina J MacArthur, Abigail Taylor, Alexandra McAleenan, Sarah Dawson, José A López-López, Julian P T Higgins, Sean Cowlishaw, Anne Lingford-Hughes, Matthew Hickman, David Kessler
Journal: BMJ (2020)

Abstract Objective To determine the most effective interventions in recently detoxified, alcohol dependent patients for implementation in primary care. Design Systematic review and network meta-analysis. Data sources Medline, Embase, PsycINFO, Cochrane CENTRAL, ClinicalTrials.gov, and the World Health Organization’s International Clinical Trials Registry Platform. Study selection Randomised controlled trials comparing two or more interventions that could be used in primary care. The population was patients with alcohol dependency diagnosed by standardised clinical tools and who became detoxified within four weeks. Data extraction Outcomes of interest were continuous abstinence from alcohol (effectiveness) and all cause dropouts (as a proxy for acceptability) at least 12 weeks after start of intervention. Results 64 trials (43 interventions) were included. The median probability of abstinence across placebo arms was 25%. Compared with placebo, the only intervention associated with increased probability of abstinence and moderate certainty evidence was acamprosate (odds ratio 1.86, 95% confidence interval 1.49 to 2.33, corresponding to an absolute probability of 38%). Of the 62 included trials that reported all cause dropouts, interventions associated with a reduced number of dropouts compared with placebo (probability 50%) and moderate certainty of evidence were acamprosate (0.73, 0.62 to 0.86; 42%), naltrexone (0.70, 0.50 to 0.98; 41%), and acamprosate-naltrexone (0.30, 0.13 to 0.67; 17%). Acamprosate was the only intervention associated with moderate confidence in the evidence of effectiveness and acceptability up to 12 months. It is uncertain whether other interventions can help maintain abstinence and reduce dropouts because of low confidence in the evidence. Conclusions Evidence is lacking for benefit from interventions that could be implemented in primary care settings for alcohol abstinence, other than for acamprosate. More evidence from high quality randomised controlled trials is needed, as are strategies using combined interventions (combinations of drug interventions or drug and psychosocial interventions) to improve treatment of alcohol dependency in primary care. Systematic review registration PROSPERO CRD42016049779.
T Cell‐Mediated Transport of Polymer Nanoparticles across the Blood–Brain Barrier
Authors: Maxime Ayer, Markus Schuster, Isabelle Gruber, Claudia Blatti, Elisa Kaba, Gaby Enzmann, Olivier Burri, Romain Guiet, Arne Seitz, Britta Engelhardt, Harm‐Anton Klok
Journal: Advanced Healthcare Materials (2020)

Delivery of therapeutics to the central nervous system (CNS) is challenging due to the presence of the blood-brain barrier (BBB). Amongst various approaches that have been explored to facilitate drug delivery to the CNS, the use of cells that have the intrinsic ability to cross the BBB is relatively unexplored, yet very attractive. This paper presents a first proof-of-concept that demonstrates the feasibility of activated effector/memory CD4