tbuckley/cabot-search huggingface dataset:
Abstract P237: Measuring Cognition in the Atherosclerosis Risk in Communities (ARIC) Study Cohort: An approach to Account for Informative Attrition
Authors: Lisa M Wruck, Alvaro Alonso, Marilyn Albert, Josef Coresh, David Couper, Rebecca Gottesman, David S Knopman, Wayne Rosamond, A. R Sharrett, Thomas H Mosley
Journal: Circulation (2015)

Introduction: Understanding the role of risk factors associated with accelerated cognitive decline has important public health relevance for the aging US population. To test hypotheses that mid-life cardiovascular (CV) risk factors increase risk of dementia in old age, the Atherosclerosis Risk in Communities (ARIC) cohort was evaluated for dementia in 2011-2013. Anticipating challenges of complete dementia ascertainment in an elderly population, supplementary data sources were collected to aid analysis accounting for potentially informative attrition. Methods: ARIC enrolled 15,792 participants 45-64 years old at baseline (1987-1989) from four US communities and collected baseline CV exposure data. A complete neurocognitive battery including informant interview was completed 2011-2013, yielding an algorithmic diagnosis of dementia, mild cognitive impairment (MCI) or normal cognition. Cognitively impaired and a random sample of cognitively normal were selected for further clinical evaluation. Syndromic diagnoses (dementia/MCI/normal) and etiologic diagnoses were made by a panel of experts using standardized criteria. Standardized protocols, timely reports of reviewer reliability, ongoing training of reviewers and a web-based data management system were developed to ensure reliability, consistency and efficiency of data collection and review. Living participants not attending the visit were asked to complete the Telephone Interview for Cognitive Status (TICS). Based on dementia discharge codes and death codes identified during cohort surveillance, interviewer impression of hearing loss or cognitive impairment or need for a proxy during semi-annual calls, or random sampling, participants refusing the TICS are eligible for proxy dementia interview. Medicare claims are being examined to identify missed dementia discharge codes. Results: Of 11,017 participants alive as of 2011, 6495 (59%) completed the neurocognitive battery; 2937 of these (45%) were selected for, and completed, additional clinical assessments and classification by committee (algorithmic or reviewer diagnosis: dementia 5%, MCI 21%). Of the 4522 participants who did not undergo the neurocognitive battery, 1463 (32%) completed the TICS (dementia 7%), while 1627 of the remaining participants were eligible for proxy calls (903 completed to date, dementia 58%). Conclusions: Participants who were not examined were more likely to be cognitively impaired, highlighting the importance of collecting supplementary data to support analyses of midlife CV risk factors accounting for informative attrition. Collection of exam data in an elderly cohort is difficult and requires a multi-pronged approach, especially for an outcome highly correlated with attrition. The strategy described here could be applied in other settings.
DNA Nanoparticles: Highly PEGylated DNA Nanoparticles Provide Uniform and Widespread Gene Transfer in the Brain (Adv. Healthcare Mater. 7/2015)
Authors: Panagiotis Mastorakos, Clark Zhang, Sneha Berry, Yumin Oh, Seulki Lee, Charles G. Eberhart, Graeme F. Woodworth, Jung Soo Suk, Justin Hanes
Journal: Advanced Healthcare Materials (2015)

On page 1023 J. S. Suk, J. Hanes, and team demonstrate how exceptionally well PEGylated DNA nanoparticles are able to traverse through the brain extracellular space avoiding interactions with the extracellular matrix (ECM) components. Following convection enhanced delivery, these brain-penetrating nanoparticles uniformly distribute and provide widespread transgene expression throughout the brain parenchyma. In contrast, conventionally designed DNA nanoparticles rapidly aggregate and remain confined to the point of administration.
Abstract 12085: Quantitative Adenosine Stress Myocardial Perfusion Computed Tomography: A 4-Fold Radiation Dose Reduction Using a Time Adaptive Filter (TAF)
Authors: Juan C Ramirez-Giraldo, Yu Liu, Jill L Anderson, James D Krier, Kay D Parker, Jodie A Christner, Lilach O Lerman, Erik L Ritman, Cynthia H McCollough
Journal: Circulation (2011)

Introduction: Integration of myocardial perfusion (MP) computed tomography into routine clinical practice is limited by high radiation dose. However, reduced dose leads to increased image noise and...
Effect of dichloroacetate in combination with chemotherapy on human lung cancer cells
Authors: G. A. Otterson, L. Wang, X. Wu, W. Duan, L. Gao, M. J. Karpenko, M. A. Villalona-Calero
Journal: Journal of Clinical Oncology (2008)

14637 Background: Dichloroacetate (DCA) is a small molecule that blocks mitochondrial pyruvate dehydrogenase kinase (PDK) shifting metabolism from glycolysis to glucose oxidation. The compound has been used in patients with certain inherited mitochondrial diseases, but it has not yet been studied in patients with cancer. Recently, it has been shown that DCA has anticancer properties with minimal toxicity in animal models. We hypothesized that the shift in metabolism caused by DCA on mitochondrial PDK would enhance the effects of cytotoxic chemotherapy on lung cancer cells. Methods: In order to evaluate the effect of DCA alone and in combination with cytotoxic chemotherapy on cancer growth, induction of apoptosis in human non-small cell cancer, two non-small cell lung cancer cell lines (A549 and H719) were subjected to different concentrations of DCA alone and in combination with different chemotherapeutic agents (paclitaxel, cisplatin, mitomycin C, etoposide) in vitro. Analysis included MTT assay for proliferation, Annexin V staining for apoptosis induction, and Caspase 3 activation. Results: Our results demonstrated that DCA had no effect on inducing cellular apoptosis, decreasing proliferation, and inhibiting growth rate. When combined with cytotoxic chemotherapy, we did not demonstrate additive activity in these assays when combined with paclitaxel, etoposide or cisplatin. Iinterestingly, further study revealed DCA enhanced the anti-proliferative activity of nanomolar concentrations of Mitomycin C in H719 cells (though no effect was seen on A549 cells). Conclusions: Our results suggest that DCA may enhance the activity of certain chemotherapeutic agents on cancer cells. Further studies to address the effect of DCA in combination with traditional chemotherapies on human cancer may be warranted both in vitro and in vivo. No significant financial relationships to disclose.
Abstract 8926: Rosiglitazone Acutely Improves Flow Mediated Dilation and Favorably Alters Endothelial Microparticle and Progenitor Cell Numbers in Euglycemic, Senescent Monkeys
Authors: Sharon A Sokolowski, Chunli Huang, Richard L Schroeder, Andrew H Smith, David A Beebe, Miao Wang, Delvin R Knight
Journal: Circulation (2011)

Background: Rosiglitazone, 6 hours after dosing, rapidly increases endothelial-dependent flow mediated dilation (FMD) in subjects with healthy endothelium. Whether this acute improvement in FMD occurs in the presence of endothelial dysfunction is unknown. We test the hypothesis that rosiglitazone acutely improves FMD in senescent monkeys with endothelial dysfunction and that the improvement coincides with favorable changes in circulating biomarkers of endothelial health, endothelial progenitor cells (EPC) and endothelial microparticles (EMP). Euglycemic monkeys were used to avoid rosiglitazone’s glucose-lowering effects. Methods and Results: In a crossover design, 6 fasted M. fascicularis monkeys (5M/1F; 17 ± 1 yr) were dosed ≥2 weeks apart with vehicle or rosiglitazone at a dose (1 mg/kg, PO) that did not affect baseline hemodynamics, fasting plasma glucose (65 ± 6 mg/dL), insulin (10 ± 3 µlU/mL), total cholesterol (79 ± 7 mg/dL) or triglycerides (59 ± 6 mg/dL). EPC and EMP were sampled 6 h after dosing and measured by flow cytometry. Monkeys were then sedated (midazolam + torbugesic) and baseline femoral artery diameter (4mm segment) measured by ultrasonography. FMD was calculated as the peak %change from baseline following a 5-minute cessation of blood flow below the knee. FMD was lower in these monkeys (17.6 ± 1.3%) vs. young adults (≥25%). Rosiglitazone (vs. vehicle) increased (p&lt;0.01) FMD to 21.3 ± 1.6% (vs.16.9 ± 1.4%) without affecting baseline diameter (1.52 ± 0.04 vs.1.51 ± 0.04 mm). Rosiglitazone (vs. vehicle) increased (p&lt;0.01) EPC [CD45- CD31+ CD34+ VEGFR2+] to 7116 ± 1296 (vs. 4786 ± 1102) cells/ml and decreased (p&lt;0.04) EMP [CD45- CD42a- CD54(ICAM-1)+] to 26669 ± 11112 (vs. 62245 ± 9772) EMP/ml; EMP [CD45- CD42a- CD105(endoglin)+] and EMP [CD45- CD42a- CD144(VE-cadherin)+] also trended lower. (Mean ± SEM; paired t-test). Conclusion: Rosiglitazone acutely improves the endothelial dysfunction in senescent monkeys. This increased FMD is independent of its metabolic effects on glucose and lipids and coincides with stimulation of EPC and with suppression of EMP linked to endothelial cell adhesion and potentially apoptosis. Whether these EPC and EMP changes directly contribute to the enhanced endothelial function warrants further study.
Chemotherapy-Derived Inflammatory Responses Accelerate the Formation of Immunosuppressive Myeloid Cells in the Tissue Microenvironment of Human Pancreatic Cancer
Authors: Shintaro Takeuchi, Muhammad Baghdadi, Takahiro Tsuchikawa, Haruka Wada, Toru Nakamura, Hirotake Abe, Sayaka Nakanishi, Yuu Usui, Kohtaro Higuchi, Mizuna Takahashi, Kazuho Inoko, Syoki Sato, Hironobu Takano, Toshiaki Shichinohe, Ken-ichiro Seino, Satoshi Hirano
Journal: Cancer Research (2015)

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic malignancies. PDAC builds a tumor microenvironment that plays critical roles in tumor progression and metastasis. However, the relationship between chemotherapy and modulation of PDAC-induced tumor microenvironment remains poorly understood. In this study, we report a role of chemotherapy-derived inflammatory response in the enrichment of PDAC microenvironment with immunosuppressive myeloid cells. Granulocyte macrophage colony-stimulating factor (GM-CSF) is a major cytokine associated with oncogenic KRAS in PDAC cells. GM-CSF production was significantly enhanced in various PDAC cell lines or PDAC tumor tissues from patients after treatment with chemotherapy, which induced the differentiation of monocytes into myeloid-derived suppressor cells (MDSC). Furthermore, blockade of GM-CSF with monoclonal antibodies helped to restore T-cell proliferation when cocultured with monocytes stimulated with tumor supernatants. GM-CSF expression was also observed in primary tumors and correlated with poor prognosis in PDAC patients. Together, these results describe a role of GM-CSF in the modification of chemotherapy-treated PDAC microenvironment and suggest that the targeting of GM-CSF may benefit PDAC patients' refractory to current anticancer regimens by defeating MDSC-mediated immune escape.
What are the functional consequences of neurocognitive deficits in schizophrenia?
Authors: M F Green
Journal: American Journal of Psychiatry (1996)

It has been well established that schizophrenic patients have neurocognitive deficits, but it is not known how these deficits influence the daily lives of patients. The goal of this review was to determine which, if any, neurocognitive deficits restrict the functioning of schizophrenic patients in the outside world.The author reviewed studies that have evaluated neurocognitive measures as predictors and correlates of functional outcome for schizophrenic patients. The review included 1) studies that have prospectively evaluated specific aspects of neurocognition and community (e.g., social and vocational) functioning (six studies), 2) all known studies of neurocognitive correlates of social problem solving (five studies), and 3) all known studies of neurocognitive correlates and predictors of psychosocial skill acquisition (six studies).Despite wide variation among studies in the selection of neurocognitive measures, some consistencies emerged. The most consistent finding was that verbal memory was associated with all types of functional outcome. Vigilance was related to social problem solving and skill acquisition. Card sorting predicted community functioning but not social problem solving. Negative symptoms were associated with social problem solving but not skill acquisition. Notably, psychotic symptoms were not significantly associated with outcome measures in any of the studies reviewed.Verbal memory and vigilance appear to be necessary for adequate functional outcome. Deficiencies in these areas may prevent patients from attaining optimal adaptation and hence act as "neurocognitive rate-limiting factors." On the basis of this review of the literature, a series of hypotheses are offered for follow-up studies.
Abstract 1060: Epigenome-wide DNA methylation profiling of lung tumors from asbestos-exposed patients
Authors: Eeva M. Kettunen, Hector Hernandez-Vargas, Marie-Pierre Cros, Geoffroy Durand, Florence Le Calvez-Kelm, Henrik Wolff, Kaisa Salmenkivi, Sisko L. Anttila, Zdenko Herceg, Kirsti Husgafvel-Pursiainen
Journal: Cancer Research (2015)

Abstract Introduction and objectives. Epigenetic modifications such as changes in DNA methylation have been shown as response to many toxic exposures. However, not much is known about the role of epigenetics in human lung carcinogenesis associated with asbestos exposure. Here, we explored the epigenome-wide DNA methylation (DNA methylome) patterns in lung tumors focused on asbestos-exposed and non-exposed patients who were mostly smokers. We sought to investigate whether methylation markers in lung cancer associate with exposure (asbestos, tobacco smoke) and clinico-pathological features. Study design, subjects, and methods. The DNA methylome was examined by Illumina Infinium 450K HumanMethylation technology covering more than 450 000 CpG sites. Validation experiments were done by pyrosequencing. DNA methylation was studied in lung tumors and normal lung as matched pairs obtained from 28 patients from lung surgery in Helsinki during years 1988-1996. Detailed data on the patients’ work and smoking histories, pulmonary fiber counts (14 asbestos-exposed and 14 non-exposed), and clinical data were available. As controls, normal lung specimens from patients with non-malignant lung disease were studied for genome-wide DNA methylation. Results. DNA methylation profiles differed in relation to sample type, tumor histology and exposure status. We identified more than 10.000 methylation variable positions (MVPs) that differed (adjusted P &amp;lt; 0.05) between lung tumors and matched normal lung. Differential methylation in 14 MVPs were significantly associated with asbestos exposure in lung tumor tissue whereas more than 100 MVPs were suggested as smoking-related. Differential methylation of genes such as those involved in cell stress and inflammation, cellular energy and lipid metabolism, and protein degradation processes were observed in lung tumors. Conclusions. Our analysis suggests that methylation profiles were globally affected in lung tumors in comparison to matched normal lung. We also found associations to asbestos exposure and tobacco smoking, suggesting a role for these exposures in modification of DNA methylome profiles. Citation Format: Eeva M. Kettunen, Hector Hernandez-Vargas, Marie-Pierre Cros, Geoffroy Durand, Florence Le Calvez-Kelm, Henrik Wolff, Kaisa Salmenkivi, Sisko L. Anttila, Zdenko Herceg, Kirsti Husgafvel-Pursiainen. Epigenome-wide DNA methylation profiling of lung tumors from asbestos-exposed patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1060. doi:10.1158/1538-7445.AM2015-1060
Specific detection of carcinoembryonic antigen-expressing tumor cells in bone marrow aspirates by polymerase chain reaction.
Authors: M Gerhard, H Juhl, H Kalthoff, H W Schreiber, C Wagener, M Neumaier
Journal: Journal of Clinical Oncology (1994)

PURPOSE To establish a sensitive assay for the specific detection of carcinoembryonic antigen (CEA)-expressing tumor cells in the bone marrow of patients with colorectal cancer and other CEA-positive carcinomas. PATIENTS AND METHODS A CEA-specific nested reverse transcriptase (RT) polymerase chain reaction (PCR) assay was developed and optimized using limiting dilutions of a CEA-positive cancer cell line mixed with normal bone marrow cell specimens. The optimized test was then used to examine bone marrow samples obtained from 15 patients with abdominal carcinomas (colorectal, n = 10; pancreatic, n = 3; gastric, n = 2) and six patients with breast cancer. Specificity was assessed by examination of 56 negative controls (malignant hematologic disease, n = 28; nonmalignant disease conditions, n = 5; healthy bone marrow donors, n = 8; normal peripheral-blood samples, n = 15). For 11 patients with abdominal carcinomas, immunostaining evaluations were performed using an anti-CEA and an anticytokeratin antibody, and the results compared with the nested PCR assay. RESULTS In the sensitivity calibration system, single CEA-expressing tumor cells were detected in 2 to 5 x 10(7) normal bone marrow cells. All 56 control samples failed to amplify. This demonstrates that mRNAs coding for highly homologous CEA-related antigens expressed by various lineages of blood cells do not interfere. Bone marrow samples from 10 of 15 patients with abdominal cancers and four of six breast cancer patients scored positive, indicating micrometastatic bone disease. Four of 11 samples from the gastrointestinal cancer patients were found to be positive by the PCR method, but were negative with the immunocytology method. CONCLUSION Since approximately 30% of the colorectal carcinoma patients that score negative in immunocytology staining of bone marrow samples have been reported to relapse, earlier diagnosis of the presence of malignant cells is needed. Our result that samples scoring positive in the described CEA-specific PCR test remained negative by two immunostaining methods suggests a higher sensitivity. We conclude that PCR amplification of CEA mRNA may lead to an earlier diagnosis of micrometastatic bone disease in patients with CEA-expressing carcinomas.
Systems-based analysis of responses to stimulation or inhibition of EGF receptor signaling in breast cancer cells
Authors: Olga Mirzoeva, Jing Zhang, Richard Neve, Heidi Feiler, Ju Han, Wen-Lin Kuo, Nora Bayani, Zhi Hu, Yinhui Guan, Debopriya Das, Laura Heiser, Doris Siwak, Merrill Knapp, Gordon Mills, Keith Ladaroute, Carolyn Talcott, Bahram Parvin, Paul Spellman, Frank McCormick, Joe Gray, W. Korn
Journal: Cancer Research (2007)

4427  Comprehensive assessment of molecular and cellular responses to stimulation or inhibition of the EGFR pathway is a prerequisite for the generation and optimization of computerized models of this pathway. Pathway Logic is a rule-based model that uses rewrite logic to symbolically represent biological processes. To expand the rule set of this model, we performed an extensive temporal analysis of molecular and cellular responses to EGF stimulation and MEK inhibition in two breast cancer cell lines (T47D and MBA-MD-231). RNA expression array analyses and reverse-phase protein lysate array analyses were performed. In addition, changes in cell cycle distribution, cell viability, and apoptosis rates were measured. Unsupervised cluster analysis was performed and the canonical-pathway based analysis system GenMAPP was used to map observed changes onto known pathways. Expected responses were clearly reproduced, including the early-growth response to EGF stimulation that includes activation of the transcription factors c-Jun/c-Fos or the activation of dual-specificity phosphatases, which are known to be negative regulators of Ras-MEK-ERK signaling. In addition, evidence for pathway crosstalk and feedback loops was found. For example, increased expression of EGF receptor RNA and possible activation of transcripition factors down-stream of PI3-kinase following MEK inhibition were found. Since the time-course experiment was also suggestive of cross-talk between Ras-MEK-ERK signaling and PI3-kinase as well as the TGF-beta pathway, we are currently testing the role of these pathways as mediators of therapeutic resistance to MEK inhibition. Data from these analyses are being used to expand the rule set of the Pathway Logic model thus allowing for better prediction of pathway responses to targeted interventions into signal transduction processes.
Prognostic value of thyroid-stimulating hormone within reference range in patients with coronary artery disease
Authors: Gjin Ndrepepa, Siegmund Braun, Katharina Mayer, Salvatore Cassese, Massimiliano Fusaro, Robert A. Byrne, Petra Hoppmann, Heribert Schunkert, Karl-Ludwig Laugwitz, Adnan Kastrati
Journal: Metabolism (2015)
Quality assessment of Chrysanthemum indicum Flower by simultaneous quantification of six major ingredients using a single reference standard combined with HPLC fingerprint analysis
Authors: Jiao He, Xiaoxue Wu, Yali Kuang, Tianyang Wang, Kaishun Bi, Qing Li
Journal: Asian Journal of Pharmaceutical Sciences (2015)

Chrysanthemum indicum Flower is usually consumed as functional food. This paper described an improved total quality assessment method for Chrysanthemum indicum Flower by simultaneous quantitation using a single standard to determine multi-components method combined with high performance liquid chromatography fingerprint analysis. Six main components of Chrysanthemum indicum Flower including two flavonoids and four phenolic acids were simultaneously quantified using linarin as the internal reference standard. The method was fully validated with respect to linearity, precision, accuracy, robustness and stability. The validated method was successfully applied to the analysis of thirty three batches of Chrysanthemum indicum Flower samples. Under the same chromatographic conditions, fingerprint analysis in combination with Similarity analysis and principal component analysis was performed to identify the samples from different regions. In general, an effective assessment using a single standard to determinate multi-components method combined with fingerprint analysis make the reliable qualitation and quantitation analysis of Chrysanthemum indicum Flower available.
The Measurement of Pulmonary Flow Reserve for Early Detection of Pulmonary Vascular Disease
Authors: Rahn Ilsar
Journal: Circulation (2008)

Abstract 501 Rahn Ilsar, Chirapan Chawantanpipat, Kim H Chan, Richard Waugh, Annemarie Hennessy, David S Celermajer, Martin K Ng, Royal Prince Alfred Hosp, Sydney, Australia Rahn Ilsar, 2008 Finali...