tbuckley/cabot-search huggingface dataset:
SP0136 Case Validation in Research Using Large Databases
Authors: L. García Rodríguez
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Computerized healthcare databases (CHCD) have been increasingly used in epidemiologic research and have become the single most used source of information in pharmacoepidemiology. A key feature in the selection of a computerized database for research is completeness and validity of recorded data. The Clinical Practice Research Datalink (CPRD - previously known as GPRD) and The Health Improvement Network (THIN) are two primary care UK databases that have an extensive track record of peer-reviewed studies. Yet, a large number of published research almost exclusively makes use of automated data. The validation process of a database is complex and the resources required to implement a study protocol using CHCD will vary widely depending on the need and amount of validation required. Validation process can be grouped under three sequential process: first, a computerized search to identify study population and patients with recorded outcomes: second, a manual review of patient profiles without and/or with free text information of primary care records: finally, a questionnaire sent to primary care physicians to confirm the validity of the studied outcome. Personel and time resources to complete these validation steps can be huge, but the quality and validity of the resutling research can be substantially improved. If researchers decide to skip this demanding validation process, then they should be ready to accept that journal reviewers and readers (when published) have legitimate doubts about the validity and relevance of their findings. <h3>Disclosure of Interest</h3> None Declared
MS-06 * DEFINING THE OPTIMAL FOLLOW-UP SCHEDULE FOLLOWING SURGICAL RESECTION OF GRADE I MENINGIOMA
Authors: E. Chavredakis, A. Brodbelt, M. Jenkinson
Journal: Neuro-Oncology (2014)

BACKROUND: Extent resection is the standard practice for predicting recurrence/progression in meningioma. A number of studies have questioned the use of the Simpson grading system in modern neurosurgery. The aim remains to obtain an accurate prediction of recurrence risk so that a safe follow up/imaging schedule can be implemented. METHODS: Retrospective study of all resected WHO grade 1 meningioma at the Walton Centre NHS Foundation Trust from 2002 - 2007. Anatomical location, Simpson clearance, outpatient and imaging follow up and recurrence/progression time and actions were recorded. Descriptive statistics and Kaplan-Meier curves were plotted to calculate recurrence/progression free time by anatomic location, Simpson grading, gross total resection (GTR = Simpson 1-3) and subtotal resection (STR = Simpson 4-5). RESULTS: 145 records were included (74.5% females). Tumour location was: parasagittal/ parafalcine 24.1%; convexity 22.8%;and skull base 53.1%. Simpson resection was grade 1: 21.4%; grade 2: 42.8%; and grade 4: 35.2%. GTR was 64.1% and STR 35.9%. Median follow up was 60 months. Median number of follow-up MRI and clinic appointments was 5. Recurrence/progression occurred in 11.7%, 3 convexity with median reccurence/ progression time 68.3 months, 2 parasagittal/ parafalcine, median time of 24 months and 12 skull base with a median time of 53.3 months. PFS was 96.8% for Simpson 1, 100% for Simpson 2 and 82.4% for Simpson 4. PFS for GTR was 98.9% and for STR was 82.7% (p = 0.005). CONCLUSIONS: Extent of resection (GTR or STR) determines risk of recurrence. For convexity and parasagittal meningioma with GTR, follow-up MRI is sufficient for years 1, 2 and 5. Skull base tumours and STR in any location should have annual MRI.
American Academy of Neurology Guidelines and the Neurologic Determination of Death
Authors: Mohamed Y. Rady, Joseph L. Verheijde
Journal: JAMA Neurology (2016)

To the Editor Greer et al1 analyzed compliance of hospital protocols on brain death (BD) determination with the 2010 American Academy of Neurology (AAN) guidelines. They posited that this neurologic standard is 100% accurate. We comment on the accuracy claim.
Abstract 1308: ERRβ ligand DY131 regulation of the hedgehog signaling pathway by modulation of Akt phosphorylation.
Authors: Yuan Lu, Benjamin R. Merideth, Hui Lin, Dennis B. Lubahn
Journal: Cancer Research (2013)

Abstract Nuclear receptor family member, Estrogen Related Receptor β (ERRβ), and hedgehog (Hh)-signaling are reported to be significant for both tumorigenesis and stem cell maintenance. ERRβ itself is a crucial factor in inducing pluripotent stem cells. Here we investigate the hypothesis that ERRβ can interact with Hh signaling pathway, and modulation of ERRβ can influence Hh signaling. NIH3T3 and HEK293 cells, transfected with a Gli response element driven luciferase reporter, were treated with different concentrations of DY131, a synthetic ERRβ ligand, in the presence or absence of exogenous ERRβ. We monitored the Gli reporter activity, as well as Gli1, Akt and phosphorylated Akt via western blot. Results: We found that DY131 inhibited Hh signaling activity when the pathway was activated by hedgehog peptide-conditioned medium, or the Smoothened Agonist (SAG), with an IC50 of 500nM. We also found that in HEK293 cells, where Gli reporter activity cannot be activated by either conditioned medium or SAG, DY131 dose dependently increased both endogenous and exogenous Gli1-induced reporter activity up to 4 fold. In addition, the transfection of ERRβ potentiated DY131’s effect on Gli reporter activity up to 7 fold. Western blot results, which are consistent with Gli reporter activity in both cell lines, showed that when Hh signaling is activated by Hedgehog peptide-conditioned medium, DY131 decreased Gli1 protein concentration; however when Hh signaling is not activated by conditioned medium, DY131 increases the concentration of Gli1 protein. Phosphorylated Akt, which is a non-canonical activator of Gli1, is up-regulated when Gli1 concentration increases, and down-regulated when the cells are treated with DY131. Conclusion: Our results suggest a new level of regulation by ERRβ on the Hh-signaling pathway. ERRβ, induced by DY131, can modulate Akt's regulation of Gli1. Additionally, our results indicate that modulation of ERRβ, via ERRβ selective drugs like DY131, may serve as a new target for Hh-driven cancer treatment. Citation Format: Yuan Lu, Benjamin R. Merideth, Hui Lin, Dennis B. Lubahn. ERRβ ligand DY131 regulation of the hedgehog signaling pathway by modulation of Akt phosphorylation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1308. doi:10.1158/1538-7445.AM2013-1308
Abstract 966: Snail mediated transcriptional repression and EMT requires zinc-finger and SNAG domain directed phosphorylation: Identification of the kinases and evaluation as therapeutic targets
Authors: Frank J. Rauscher, Zhaoyuan Hou, Hongzhuang Peng, David E. White, Colleen Wood
Journal: Cancer Research (2011)

Abstract The Snail zinc-finger transcription factor is a master regulator of the Epithelial-Mesenchymal Transition (EMT) which occurs during the early steps in tumor metastasis. Snail is strongly up-regulated and causally involved in EMT: it binds directly to the promoters of genes which mediate EMT and functions largely as a repressor thereby regulating a comprehensive transcriptome which establishes and maintains the invasive mesenchymal phenotype. Snail is a marker for the malignant phenotype, prognosis and strongly predicts treatment failure, relapse and overall survival. Inhibiting the Snail pathway is a novel approach to metastasis prevention and therapeutics. We have: 1) identified the LIM protein AJUBA as a novel co-repressor for Snail-mediated EMT; 2) shown that the arginine methyltransferase 5 (PRMT5) complex is recruited to SNAIL through AJUBA and; 3) discovered that Snail/AJUBA/PRMT5 complex assembly in chromatin requires that the zinc-finger region of Snail be phosphorylated at serine/threonine residues in the DNA binding and repression domains and that these modifications are directly recognized by 14-3-3 proteins. The quaternary pSnail/AJUBA/PRMT5/14-3-3 complex is enriched at endogenous Snail target genes via ChIP. Mutation of the target amino acids Serine11 and Threonine177 to alanine concommitantly abolished: 14-3-3 binding, chromatin association of the complex, and transcriptional repression. Moreover, Snail induction of EMT and metastasis was inhibited. These studies suggest that targeting the Snail directed kinases for inhibition is a viable strategy for controlling tumor progression and metastasis. The Identification of these kinases and their regulation during tumor progression will be presented. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 966. doi:10.1158/1538-7445.AM2011-966
Abstract 4269: Human Epidermal Growth Factor (EGF) supresses Tumor Necrosis Factor-a (TNF-a)-mediated induction of Caspase-1, STAT1 and Apoptosis in human cervical carcinoma cells.
Authors: Osman N. Ozes
Journal: Cancer Research (2013)

Abstract Background: Members of Human Epidermal Growth Factor Receptors are over-expressed in variety of cancers. The EGFR-mediated activation of signal transduction pathways ultimately induce cellular growth, supress apoptosis and can cause tumor malignancy. On the contrary, TNF-α induces the expression of numerous genes which contribute to the inhibition of growth and the induction of apoptosis. Therefore, we tested the impact of EGF on TNF-α-induced expression of Caspase-1, activation of STAT1 and induction of apoptosis on human cervical carcinoma cells, (ME180). Results: Treatment of ME180 cells with TNF-α (10 ng/ml) induced the expression of Caspase-1 in a time dependent manner. Also, pre-treatment of these cells with EGF (10ng/ml) completely inhibited TNF-induced Caspase-1 induction. Since Caspase-1 induction is mediated by STAT1, the levels of STAT1 activation by TNF was determined. It was found that TNF induces STAT1 activation in these cells. However, pre-treatment of ME180 cells with EGF completely inhibited TNF-α-mediated activation of STAT1. Parallel to these findings, pre-treatment of ME180 cells with EGF for 1 hour completely inhibited TNF-induced apoptosis in these cells. Conclusion: These results suggest that tumor microenvironment created by the tumor or surrounding cells are important in controlling the growth and apoptosis of cancer cells. Therefore, abundance of growth factors and pro-apoptotic cytokines may determine the fate of tumor behavior. Citation Format: Osman N. Ozes. Human Epidermal Growth Factor (EGF) supresses Tumor Necrosis Factor-a (TNF-a)-mediated induction of Caspase-1, STAT1 and Apoptosis in human cervical carcinoma cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4269. doi:10.1158/1538-7445.AM2013-4269
Abstract 3022: Disruption of the nuclear matrix attachment domain of the DNA replication factor Ciz1 in common solid tumors and its potential as a biomarker
Authors: Heather Sercombe, Gillian Higgins, Jennifer Munkley, Nikki Copeland, Katherine Roper, Faisal Abdel Rahman, Justin Ainscough, Dawn Coverley
Journal: Cancer Research (2011)

Abstract The DNA replication protein Ciz1 promotes initiation of mammalian DNA replication in cooperation with cyclin A-dependent kinase, most likely by delivery cyclin A to sites where cyclin E-dependent pre-replication complex assembly has taken place. Normally, Ciz1 is anchored within nuclear matrix-associated foci that co-localize with sites of DNA replication, but in the absence of anchor domain Ciz1 retains the ability to promote initiation of DNA replication in isolated nuclei so attachment to the nuclear matrix is not essential for function. Here, we show that expression of DNA replication and nuclear matrix anchor domains of Ciz1 are uncoupled and uneven at the transcript level in a panel of common cancer cell lines, giving rise to excess DNA replication domain protein that is not attached to the nuclear matrix. Moreover Ciz1 domain expression is also uncoupled in a wide range of common solid tumours, including breast and lung, so that anchor domain transcript is elevated over control tissues, and exceeds replication domain in all primary stage I, II and III tumours tested. Notably, more than half of all stage IV tumours tested resemble established cell lines, having more replication domain than anchor domain. In cell based assays, recombinant anchor domain protein interferes with attachment of endogenous Ciz1 to the nuclear matrix, revealing a dominant negative effect that also impacts on nuclear matrix-recruitment of a key component of the pre-replication complex, Cdc6. This shows that Ciz1 normally plays a role in localizing Cdc6 to the nuclear matrix and suggests that cancer-associated uncoupled expression influences recruitment of mammalian pre-replication complexes to the nuclear matrix. These findings implicate spatially unconstrained DNA replication as a source of nuclear disorder in cancer cells. We identified a variant Ciz1 isoform with alterations in nuclear matrix attachment domain and tumour-restricted expression. Variant Ciz1 is elevated at the transcript and protein level with high frequency in small cell lung tumours, and with lower frequency in a range of other tumour types. Selective suppression of variant Ciz1 expression using inducible shRNA restricts proliferation of lung cancer cells that express it in vitro and in vivo, identifying a novel, exploitable therapeutic target with potential application in the treatment of lung cancer. Recent evidence will also be presented on the application of variant Ciz1 as a serum biomarker. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3022. doi:10.1158/1538-7445.AM2011-3022
PREDICTORS OF CARDIAC MAGNETIC RESONANCE-ASSESSED REVERSE REMODELING IN NON-ISCHEMIC DILATED CARDIOMYOPATHY
Authors: Giuseppe Vergaro, Lorenzo Nesti, Andrea Barison, Concetta Prontera, Silvia Masotti, Giovanni Donato Aquaro, Aldo Clerico, Roberta Poletti, Claudio Passino, Michele Emdin
Journal: Journal of the American College of Cardiology (2016)
Aspergillus Fumigatus (Af) Induced Airway Epithelial Accumulation and Decreased Lymph Node Homing of Myeloid Dentritic Cells (DC) in the Lung of Mice with Chronic Granulomatous Disease (CGD)
Authors: Lisa R. Forbes, Akshit Gupta, Blerian Kolkalari, Imre Redai, Angela Haczku
Journal: Journal of Allergy and Clinical Immunology (2013)
Hepatic Hydrothorax Demonstration by Tc-99m Sulfur Colloid Ascites Scan
Authors: KENNETH A. HOLT, EDUARDO OLIVIERA, PRASHANT K. ROHATGI
Journal: Clinical Nuclear Medicine (1999)

Hepatic hydrothorax is defined as the development of a pleural effusion in patients with cirrhosis as a result of migration of ascites across defects in the diaphragm. Intraperitoneal injection of Tc-99m sulfur colloid revealed a hepatic hydrothorax in an 83-year-old man with alcoholic cirrhosis and a massive right-sided transudative pleural effusion. In such cases, medical treatment options are directed at reducing formation of ascites by fluid and salt restriction and use of diuretics. Surgical procedures that may relieve symptoms include repeated thoracenteses with possible pleurodesis, transjugular intrahepatic portosystemic shunt, and operative closure of the diaphragmatic defects.
Predicting Axillary Lymph Node Status Using Preoperative Ultrasound-Guided Fine Needle Aspiration Cytology of Radiologically Equivocal and Abnormal Nodes.
Authors: J. White, B. Hogan, F. Langlands, B. Dall, K. Horgan
Journal: Cancer Research (2009)

Abstract Introduction:The superiority of ultrasound (US) over clinical examination in the assessment of axillary nodes in patients with breast carcinoma is well recognised. Fine needle aspiration cytology (FNAC) is a quick and minimally invasive procedure to determine the status of axillary lymph nodes pre-operatively. Sentinel lymph node biopsy (SLNB) is now widely accepted as the primary axillary staging procedure in the management of early breast cancer. A negative SLNB obviates the need for more extensive axillary surgery, thereby reducing the morbidity associated with axillary node clearance (ANC) in patients with node negative breast cancer. Patients with a SLNB positive for metastasis usually require further axillary treatment, which may include completion ANC and/or radiotherapy. Improving the accuracy of pre-operative staging is desirable in reducing the number of completion ANC procedures necessitated following positive SLNB. The aim of this study is to assess the accuracy of pre-operative US-guided FNAC of radiologically equivocal or abnormal axillary lymph nodes.Method:Patients with a diagnosis of invasive breast carcinoma underwent axillary US. Those with radiologically equivocal or abnormal nodes had US-guided FNAC. Patients with a metastatic FNAC had ANC, whereas those with insufficient (i.e. no lymphocytes seen on cytology), benign or equivocal FNAC had SLNB.Results:Correlation of FNAC result and final histologyFNAC ResultN=59Node positivity N=42Inadequate54Benign173Equivocal10Suspicious11Malignant3534 The positive predictive value of suspicious or malignant cytology from a radiologically equivocal or abnormal node is 97%. The negative predictive value is 70%. US-guided FNAC used in the context has 83% sensitivity and 94% specificity.Of the five patients with radiologically equivocal or abnormal nodes and an inadequate cytology (no lymphocytes seen), four had a metastatic sentinel node biopsy.One patient had a malignant FNAC prior to neoadjuvant chemotherapy (NACT) and had benign histology on subsequent ANC. If this patient is excluded from analysis, the positive predictive value rises to 100%.Conclusion:US-guided FNAC of radiologically equivocal or abnormal axillary lymph nodes accurately predicts node positivity and can be used to avoid an unnecessary SLNB procedure.Inadequate FNAC from an equivocal or abnormal node is not sufficient evidence to recommend SLNB rather than ANC as the initial surgical axillary procedure. Patients with such findings should have a repeat US-guided FNAC before choosing to proceed with SLNB. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1031.
APPROPRIATE USE OF ECHOCARDIOGRAPHY IN PEDIATRIC CHEST PAIN
Authors: Tuan Nguyen, Michael Fundora, Elizabeth Welch, Pamela Douglas, Benjamin Eidem, Robert Campbell, Rory Weiner, Kenan Stern, Oscar Benavidez, Wyman Lai, Ritu Sachdeva, Leo Lopez
Journal: Journal of the American College of Cardiology (2016)
Abstract 3591: Efficacy and distribution of intratumoral paclitaxel given alone or in combination with doxorubicin using hydrogel in nude mice
Authors: Joo-Ho Lee, Kwang-Suck Kim, Soo-Yeon Kim, Yu Jin Kim, Ahmed M. Al-abd, Ki-Yun Hong, Soo-Chang Song, Hyo-Jeong Kuh
Journal: Cancer Research (2010)

Abstract Intralesional chemotherapy is suggested to improve local tumor control as well as systemic toxicity profile of antitumor agents against solid tumors. Thermosensitive poly-(organophosphazene) hydrogel is a novel injectable polymer that transforms from sol to gel at body temperature. In this study, we evaluated distribution and efficacy of paclitaxel (PTX) when given as intratumoral injection using the hydrogel or solution formulation in human SNU-601 tumor xenograft-bearing nude mice. Following intratumoral injection of 60 mg/kg of PTX, plasma drug concentrations were lower than 0.5 μg/ml(LOQ) for both hydrogel and solution. For PTX tumor concentration, Cmax was 1.2 folds higher and T1/2 3.7 folds longer with hydrogel compared to solution. Over 21d, AUCtumor was 1.5 folds greater in hydrogel compared to solution, indicating greater drug exposure and retention at target site. The antitumor activity of PTX (30 mg/kg) when given alone or in combination with doxorubicin (DOX, 15 mg/kg) was evaluated after intratumoral hydrogel injection in SNU-601 (Td= 21 d) and SNU-398 (Td= 5 d) xenograft models. The synergism between DOX and PTX, independent of dosage form, was observed in SNU-398, but not in SNU-601. No toxicity was observed in hydrogel group in neither single nor combination treatment. For slow-growing SNU-601 tumor, combination of PTX and DOX given in hyrogel mixture showed greater activity than that of solution. In conclusion, poly-(organophosphazene) polymer may be useful in intralesional administration of PTX to achieve greater drug exposure at target site. Also, combination of DOX and PTX, showed a potential for greater antitumor efficacy, which warrants further evaluation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3591.
Case 37-1993
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Robert L. Geggel, Eugene J. Mark
Journal: New England Journal of Medicine (1993)

Presentation of CaseA 48-year-old woman was admitted to the hospital because of a secundum atrial septal defect with severe pulmonary hypertension.A murmur was first heard when the patient was 11 years of age. At 21 years she began to experience palpitations during exercise and had auscultatory findings characteristic of an atrial septal defect. Eight years later she was dyspneic when climbing three flights of stairs and had frequent respiratory tract infections. She was seen at this hospital, and the risk of a cardiac surgical procedure was considered unacceptable. At 39 years of age supraventricular tachycardia occurred and responded . . .