tbuckley/cabot-search huggingface dataset:
Trends in Use of Daily Chest Radiographs Among US Adults Receiving Mechanical Ventilation
Authors: Hayley B. Gershengorn, Hannah Wunsch, Damon C. Scales, Gordon D. Rubenfeld
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Guidelines from December 2011 recommended against obtaining daily chest radiographs (CXRs) for patients requiring mechanical ventilation (MV). Daily CXR use for patients receiving MV in US hospitals is unknown and, if high, may represent an opportunity to reduce low-value care and unnecessary radiation. <h3>Objectives</h3> To determine frequency of daily CXR use for US patients receiving MV, assess variability across hospitals, and evaluate whether use has decreased over time. <h3>Design, Setting, and Participants</h3> Retrospective cohort study of hospitalized adults (aged ≥18 years) receiving MV for 3 days or longer. Mechanical ventilation was defined by having an<i>International Classification of Diseases, Ninth Revision, Clinical Modification</i>code of 96.7x and an MV charge on more than 1 hospital day. Hospital discharges in the Premier Perspectives database were examined from July 1, 2008, to December 31, 2014. Data analysis was conducted from July 28, 2017, to December 13, 2017. <h3>Exposures</h3> Hospital discharge date (quarter of the year) and hospital in which patients received MV. <h3>Main Outcomes and Measures</h3> The outcome was daily CXR use (up to 7 days) during MV. We used standard statistics to describe CXR use, multilevel multivariable regression modeling with adjusted median odds ratio (OR) to evaluate variability by hospital, and multivariable piecewise regression (breakpoint: fourth quarter of 2011) with adjusted OR to evaluate time trends and response to guideline recommendations. <h3>Results</h3> The primary cohort included 512 518 patients receiving MV (mean [SD] age, 63.0 [16.1] years; 46% female) in 416 hospitals, of whom 321 093 (63%) received daily CXRs. Wide variability was seen across hospitals; hospitals performed daily CXRs on a median of 66% of patients (interquartile range, 50%-77%; full range, 12%-97%). The adjusted median OR was 2.43 (95% CI, 2.29-2.59), suggesting the same patient had 2.43-fold higher odds of receiving a daily CXR if admitted to a higher- vs lower-use hospital; the odds of receiving daily CXRs were unchanged through quarter 3 of 2011 (adjusted OR, 1.00; 95% CI, 0.99-1.01), after which there was a 3% relative reduction in the odds of daily CXR use per quarter (adjusted OR, 0.97; 95% CI, 0.96-0.98). <h3>Conclusions and Relevance</h3> Three-fifths of US patients receiving MV also received daily CXRs from 2008 to 2014, although use declined slowly after new guidelines were published. The hospital at which a patient received care was associated with the odds of daily CXR receipt.
Abstract LB-289: Polarization of adipose-derived mesenchymal stem cells by toll-like receptors stimulation
Authors: Cosette M. Rivera-Cruz, Krista Huff, Marxa L. Figueiredo
Journal: Cancer Research (2018)

Abstract Mesenchymal stem cells (MSCs) are a potential tool for cell therapy because of their ability to home to injury sites, modulate immune responses, promote tissue repair, among other features. MSCs can also home to tumors, similarly to how they home to injury sites, and exert modulatory functions in the tumor microenvironment. However, the mechanisms by which MSCs affect tumor cells is not well understood, and apparent contradictory effects of MSC-tumor interactions can be found in the literature, claiming that MSCs either promote or repress tumor growth and cell migration. In recent years, it was shown that MSCs derived from bone marrow (BM-MSCs) can be polarized by Toll-like receptor (TLR) signaling into two phenotypes with opposite effects on tumor development. TLR4 signaling induces an immune activating MSC1 population shown to inhibit tumor growth and migration, whereas TLR3 signaling induces an immune suppressive MSC2 population that promotes tumor progression. Adipose-derived mesenchymal stem cells (ASCs) are important constituents of tumor microenvironments. Their ability to migrate into tumors make these cells a potential candidate for delivering immunotherapy against tumor progression. Although the MSC1 and MSC2 duality has not been reported for ASCs, we hypothesized that due to their similarity to bone marrow MSCs, that ASC share the polarization phenotype. To test our hypothesis, we stimulated, or primed, hASCs with TLR3 and TLR4 agonists and evaluated gene expression changes expected to occur, in accordance to the previously described MSC1 and MSC2 phenotypes. Upregulation of IL-8 was observed for hASCs primed towards the MSC1 phenotype. CCL5 and IP10 were upregulated in cells primed towards the MSC2 phenotype. These results suggest that a polarization of hASCs may occur in a similar way as previously shown for BM-MSCs. On the other hand, no changes were observed in the expression of TGFβ, IL-6 and other associated genes, hinting to cell lineage phenotypical differences upon TLR stimulation. In addition, some phenotypical differences have been observed across different donor cells and priming conditions, which could contribute to the immunomodulatory inconsistencies reported in the literature. Citation Format: Cosette M. Rivera-Cruz, Krista Huff, Marxa L. Figueiredo. Polarization of adipose-derived mesenchymal stem cells by toll-like receptors stimulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-289.
Abstract 3415: Cytogenetics of renal oncocytomas identify three distinct and mutually exclusive diagnostic classes of chromosome aberrations
Authors: Christopher B. Anderson, Michael Lipsky, Subhadra V. Nandula, Freeman E. Christopher, Matthews Thomas, Caitlin E. Walsh, Gen Li, Matthias Szabolcs, Mahesh M. Mansukhani, James M. McKiernan, Murty V. Vundavalli
Journal: Cancer Research (2018)

Abstract Christopher B. Anderson1, Michael Lipsky1, Subhadra V. Nandula2,3, Christopher E. Freeman2, Thomas Matthews2, Catlin Walsh2, Gen Li1, Matthias Szabolcs2, Mahesh M. Mansukhani 2, James M. McKiernan1, Vundavalli V. Murty 2 1Departments of Urology, 2Pathology and Cell Biology, Columbia University Medical Center, New York, New York; 3Cancer Genetics Inc, Rutherford, New Jersey The cytogenetic alterations in renal oncocytoma (RO) are poorly understood. We analyzed 130 consecutive RO for karyotypic alterations. Clonal chromosome abnormalities were identified in 63 (48.5%) cases, which could be categorized into 3 classes of mutually exclusive cytogenetic categories. Class 1 RO had diploid karyotypes with 11q13 rearrangement in balanced translocations with ten or more different chromosome partners in all 20 (31.7%) cases. We identified recurrent translocation partners at 5q35, 6p21, 9p24, 11p13-14 and 11q23, and confirmed that CCND1 gene rearrangement at 11q13 utilizing fluorescence in situ hybridization (FISH). Class 2 RO exhibited hypodiploid karyotypes with loss of chromosome 1 and concurrent losses of Y in males and X in females in 25 (39.7%) cases. The class 3 tumors comprising of 18 (30.2%) cases showed diverse types of abnormalities with the involvement of 2 or more chromosomes exclusive of abnormalities seen in Class 1 and 2 tumors. Furthermore, karyotypically uninformative cases were subjected to FISH analysis to identify class 1 and 2 abnormalities. In this group we found similar frequencies of CCND1 rearrangement, loss of 1 or Y as with karyotypically abnormal cases. We validated our results against 91 tumors from the Mittleman database. Correlation of clinical data with all the 3 classes of RO showed no clear evidence of overall patient survival. Our findings support the hypothesis that RO exhibit 3 principal cytogenetic categories, which may have different roles in initiation and/or progression. These cytogenetic markers provide a key tool in the diagnostic evaluation of RO. Citation Format: Christopher B. Anderson, Michael Lipsky, Subhadra V. Nandula, Freeman E. Christopher, Matthews Thomas, Caitlin E. Walsh, Gen Li, Matthias Szabolcs, Mahesh M. Mansukhani, James M. McKiernan, Murty V. Vundavalli. Cytogenetics of renal oncocytomas identify three distinct and mutually exclusive diagnostic classes of chromosome aberrations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3415.
A Case of Immune‐Mediated Liver Injury Induced by Olaparib
Authors: Manuel Tufoni, Carmen Serena Ricci, Giacomo Zaccherini
Journal: Hepatology (2018)

1Department of Medical and Surgical SciencesU.O. Semeiotica MedicaAlma Mater StudiorumUniversity of BolognaItaly *ADDRESS CORRESPONDENCE AND REPRINT REQUESTS TO: Manuel Tufoni, M.D., Department of Medical and Surgical Sciences, U.O. Semeiotica Medica, Alma Mater Studiorum University of Bologna, Via Albertoni 15, 40138 Bologna, Italy, Tel.: +39‐051‐2142931 E‐mail: [email protected]
Estimation of Cardiac Performance and Efficiency During Aortic Occlusion and Induced Muscular Activity
Authors: Arnoštfroněk, Olgahudlická
Journal: Circulation Research (1965)

1) Changes of oxygen uptake and energy output by the left ventricle were investigated during increased peripheral resistance (aortic occlusion) and increased cardiac output (induced muscular activity) in open-chest dogs under pentobarbital anaesthesia. 2) Evidence has been provided to show that energy expenditure during the isovolumic period (E1) participates significantly in the total oxygen consumption of the left ventricle (QO2). The correlation of E1 + E2 (compound energy expenditure during the whole cardiac cycle) to QO2 was closer than the correlation of the stroke work (E2) to QO2 under the experimental conditions studied. The increase of QO2 during increased peripheral resistance is due to a proportional increase of E1. 3) The determination of the total amount of compound energy released by the left ventricle, makes the estimation of the performance of the heart possible in a more specific way. Besides the classical mechanical efficiency, ηm = E2/QO2, an index of the chemomechanical turnover (comp...
Peroxisome Proliferator-Activated Receptor δ Is an Essential Transcriptional Regulator for Mitochondrial Protection and Biogenesis in Adult Heart
Authors: PeiyongWang, JianLiu, YuquanLi, SijieWu, JinwenLuo, HuanYang, RamasamySubbiah, JohnChatham, OlgaZhelyabovska, QinglinYang
Journal: Circulation Research (2010)

Rationale: Peroxisome proliferator-activated receptors (PPARs) (α, γ, and δ/β) are nuclear hormone receptors and ligand-activated transcription factors that serve as key determinants of myocardial fatty acid metabolism. Long-term cardiomyocyte-restricted PPARδ deficiency in mice leads to depressed myocardial fatty acid oxidation, bioenergetics, and premature death with lipotoxic cardiomyopathy. Objective: To explore the essential role of PPARδ in the adult heart. Methods and Results: We investigated the consequences of inducible short-term PPARδ knockout in the adult mouse heart. In addition to a substantial transcriptional downregulation of lipid metabolic proteins, short-term PPARδ knockout in the adult mouse heart attenuated cardiac expression of both Cu/Zn superoxide dismutase and manganese superoxide dismutase, leading to increased oxidative damage to the heart. Moreover, expression of key mitochondrial biogenesis determinants such as PPARγ coactivator-1 were substantially decreased in the short-term...
Abstract LB-322: Casein kinase 2 is a major regulator of medulloblastoma growth
Authors: Ryan Nitta, Sara Matilda Bolin, Ginikachi Nwagbo, Teresa Purzner, Suzana Kahn, Yoon-Jae Cho, Gordon Li
Journal: Cancer Research (2018)

Abstract Medulloblastoma (MB) is the most common malignant pediatric brain tumor, accounting for about 20% of all cases. While surgery, craniospinal irradiation, and chemotherapy have resulted in a cure rate of 70%, the surviving patients are afflicted with neurocognitive impairment, endocrine dysfunction, and a severe decrease in quality of life. Consequently, better and more effective treatments are needed to treat these young patients. Casein kinase 2 (CK2) is an intriguing therapeutic target for MB because it is dysregulated in all the MB molecular subgroups and patients with high CK2 expression have a significantly worse prognosis. To elucidate the role of CK2 in MB we transduced multiple MB cell lines with CK2 isoforms. We discovered that a CK2 isoform, CK2a, increased tumorigenesis in both the Sonic Hedgehog and Group 3 MB subgroups, while knocking down expression ameliorated MB growth. Through these transduced cell lines we also determined that CK2 can regulate MB tumorigenesis through b-catenin and potentially GLI1. Moreover, mice orthotopically injected with MB cells over-expressing CK2a or CK2b displayed a reduced survival compared to control. We extended our analysis to a CK2 inhibitor, CX-4945, which is currently undergoing phase I/II clinical trials for toxicity and safety. Treatment with CX-4945 reduced MB cell growth and also reduced expression of MGMT, a well-known regulator of temozolomide (TMZ) efficacy. Our findings were corroborated when we screened 4,000 FDA approved compounds to identify molecules that work synergistically with CX-4945. TMZ was one of the major compounds that were identified in the screen, suggesting that CX-4945 treatment can sensitize MB cells to TMZ by dysregulating MGMT. Combinatorial treatment with CX-4945 and TMZ had a synergistic effect on reducing MB tumor growth. Together, our findings suggest that CK2 is a novel therapeutic target for MB and that combining CX-4945 and TMZ can lead to a promising new MB therapy. Citation Format: Ryan Nitta, Sara Matilda Bolin, Ginikachi Nwagbo, Teresa Purzner, Suzana Kahn, Yoon-Jae Cho, Gordon Li. Casein kinase 2 is a major regulator of medulloblastoma growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-322.
Repetitive Artery-to-Artery Embolism Caused by Dynamic Movement of the Internal Carotid Artery and Mechanical Stimulation by the Hyoid Bone
Authors: KeisukeTokunaga, ToshiyukiUehara, HidekiKanamaru, HiroharuKataoka, KozueSaito, HatsueIshibashi-Ueda, RyogoShobatake, YoshifumiYamamoto, KazunoriToyoda
Journal: Circulation (2015)
Intracoronary Compared With Intravenous Bolus Abciximab Application in Patients With ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention
Authors: HolgerThiele, KathrinSchindler, JosefFriedenberger, IngoEitel, GeorgFürnau, EigkGrebe, SandraErbs, AxelLinke, SvenMöbius-Winkler, DietmarKivelitz, GerhardSchuler
Journal: Circulation (2008)

Background— Abciximab reduces major adverse cardiac events in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention (PCI). Intracoronary abciximab bolus application results in high local drug concentrations and may be more effective than a standard intravenous bolus. Methods and Results— Patients undergoing primary PCI were randomized to either intracoronary (n=77) or intravenous (n=77) bolus abciximab administration with subsequent 12-hour intravenous infusion. The primary end point was infarct size and extent of microvascular obstruction as assessed by delayed enhancement magnetic resonance. Secondary end points were ST-segment resolution at 90 minutes, Thrombolysis in Myocardial Infarction flow and perfusion grades after PCI, and the occurrence of major adverse cardiac events within 30 days. The median infarct size was 15.1% (interquartile range, 6.1% to 25.2%) in the intracoronary versus 23.4% (interquartile range, 13.6% to 33.2%) in the intravenous gro...
Abstract P040: HEALS Lifestyle intervention through African American churches to control hypertension
Authors: SunitaDodani, SahelArora, CarmenSmotherman, DaleKraemer
Journal: Circulation (2014)

Objective: African Americans (AAs) living in the “Stroke Belt” (Southeastern US including Northeast Florida) are at elevated risk for cardiovascular diseases (CVDs). An approach of proven efficacy is to target hypertension (HTN) as the major modifiable risk factor for CVDs, and to do so by evidence-based lifestyle changes. Here we present the findings of faith-based socio-culturally tailored HEALS HTN control program (modified from PREMIER and DASH diets), offered to AA church parishioners living in the food dessert areas of Duval County, Florida. Methods: Large urban church (membership > 400) volunteered for 9-month HEALS program. Four church members were trained as program leaders called CHAs-Church health Advisors, who after 10 hours of receiving training on HEALS session from PREMIER experts delivered weekly HEALS sessions to high-risk church members. 35 church members who were 25-75 year old, self-described AAs and HTN - as defined by JNC-7 were recruited. Farmer Market trucks from Clara White Missio...
Characterization of nucleoside and nucleobase transporters in a human mesothelial cell line: evaluation of nucleoside and nucleobase antimetabolites for application in malignant mesothelioma
Authors: Vijaya L. Damaraju, Deepti Damaraju, Delores Mowles, Richard C. Berendt, Michael B. Sawyer, Carol E. Cass
Journal: Cancer Research (2006)

593   Malignant mesothelioma (MM) is an aggressive cancer of the pleura that is largely refractory to surgery or radiotherapy and only moderately responsive to chemotherapy with different classes of antimetabolites. The role of nucleoside and nucleobase transporters in uptake of nucleoside and nucleobase antimetabolites in MM has not been investigated. Studies were undertaken to characterize the nucleoside and nucleobase transporter profiles of cultured MM H2052 cells and to determine their role(s) in the cytotoxic efficacy of selected nucleoside and nucleobase antimetabolites. Functional hENT1-like nucleoside transport activity was demonstrated and shown to be responsible for the uptake of uridine and gemcitabine. Reverse transcriptase-PCR, immunoblotting, and flow cytometry confirmed the presence of hENT1 in H2052 cells, and immunohistochemistry showed positive hENT1 staining in one clinical sample of MM. Nucleobase transport studies showed that hypoxanthine, but not 5-fluorouracil (5-FU), entered H2052 cells by a purine-specific sodium independent nucleobase transporter. In cytotoxicity studies, gemcitabine (a pyrimidine nucleoside) exhibited high activity against H2052 cells with an EC 50  of 60 nM whereas 5-FU (a pyrimidine nucleobase) exhibited low activity against H2052 cells with an EC 50  of 165 μM and this was further supported by the absence of 5-FU transport into H2052 cells. This work provides the basis for future preclinical studies using drug combination regimens based on observations in other model systems where combination treatments with gemcitabine and purine and pyrimidine nucleoside or nucleobase drugs were shown to be synergistic.
Detection of High-Grade Restenosis After PTCA Using Contrast-Enhanced Electron Beam CT
Authors: StephanAchenbach, WernerMoshage, KurtBachmann
Journal: Circulation (1997)

Background Contrast-enhanced electron beam computed tomography (EBCT) has been shown to permit noninvasive visualization of the coronary arteries. We determined the value of EBCT to noninvasively detect high-grade restenosis after percutaneous transluminal coronary angioplasty (PTCA). Methods and Results Fifty patients (37 to 68 years of age), were investigated by EBCT at a mean interval of 9 months after PTCA of coronary artery stenoses. Forty axial cross-sections of the heart (3-mm slice thickness, 1-mm overlap) were acquired triggered to the ECG after intravenous injection of contrast agent. Three-dimensional reconstructions of the coronary arteries were rendered with a lower threshold of 80 HU to selectively visualize the contrast-enhanced vessel lumen. EBCT results were compared with conventional quantitative coronary angiography (QCA) performed within 1 week. In 6 patients, the PTCA segment could not be evaluated because of impaired image quality. Sixteen of the remaining 44 patients had high-grade ...
Intracellular pH and Tyrosine Phosphorylation but Not Calcium Determine Shear Stress–Induced Nitric Oxide Production in Native Endothelial Cells
Authors: KazuhideAyajiki, MarkusKindermann, MarkusHecker, IngridFleming, RudiBusse
Journal: Circulation Research (1996)

Abstract Signaling pathways determining the shear stress–induced production of NO from endothelial cells in situ were investigated using a bioassay system in which shear stress was increased by inducing vasoconstriction in an endothelium-intact donor segment (rabbit iliac artery) while maintaining a constant luminal perfusion rate. Shear stress–induced NO production, as assessed by changes in the tone of a preconstricted endothelium-denuded detector ring, was biphasic and consisted of an initial transient (20- to 25-minute) Ca2+-dependent phase followed by a Ca2+-independent plateau phase, which was maintained as long as the donor segment remained constricted. Stretching the donor segments to their in vivo length abolished the initial phase without affecting the plateau phase of NO release. Inhibition of the Na+-H+ exchanger using HOE 694 elicited an intracellular acidification, which attenuated shear stress–induced NO production. The specific protein kinase C inhibitor, Ro 31-8220, was without effect, wh...
Functional Recovery of Stroke Rats Induced by Granulocyte Colony-Stimulating Factor–Stimulated Stem Cells
Authors: Woei-CherngShyu, Shinn-ZongLin, Hui-IYang, Yi-ShiuanTzeng, Cheng-YoongPang, Pao-ShengYen, HungLi
Journal: Circulation (2004)

Background— Stroke is a leading cause of death and disability worldwide; however, no effective treatment currently exists. Methods and Results— Rats receiving subcutaneous granulocyte colony-stimulating factor (G-CSF) showed less cerebral infarction, as evaluated by MRI, and improved motor performance after right middle cerebral artery ligation than vehicle-treated control rats. Subcutaneous administration of G-CSF enhanced the availability of circulating hematopoietic stem cells to the brain and their capacity for neurogenesis and angiogenesis in rats with cerebral ischemia. Conclusions— G-CSF induced increases in bone marrow cell mobilization and targeting to the brain, reducing the volume of cerebral infarction and improving neural plasticity and vascularization.