tbuckley/cabot-search huggingface dataset:
The Liverpool Lung Project: a molecular epidemiological study of early lung cancer detection
Authors: J.K. Field, J.H. Youngson
Journal: European Respiratory Journal (2002)

Lung cancer is the major cause of death from neoplastic disease in the world, and even with politically-motivated smoking cessation campaigns throughout Europe, the disease remains the major cause of death. The development of molecular epidemiological population-based research into early lung cancer detection, such as the Liverpool Lung Project (LLP), may provide a way forward. This is the first major molecular epidemiological study of detection of early lung cancer. The use of molecular epidemiological risk assessments prior to clinical diagnosis and markers of preclinical carcinogenesis in patients with a high risk of developing lung cancer will reduce the incidence of clinically-detectable lung cancer, given the appropriate intervention strategies. The aims are as follows: 1) to prepare a molecular genetic and epidemiological risk assessment model based on environmental exposures and genetic predisposition; 2) to develop an archive of specimens relating to at-risk individuals and those with lung cancer; 3) to redefine lung cancer based on molecular pathology using the fields of expression profiling, genetic instability and molecular cytogenetics; 4) to identify and assess novel markers of precarcinogenesis in high-risk populations; and 5) to facilitate the development of new treatment strategies ( e.g. chemoprevention programmes and targeted drug therapies). The LLP has two components: 1) a case-controlled study of newly-diagnosed cases of lung cancer that will provide a baseline, risk assessment; and 2) a prospective cohort study to be carried out over a 10-yr period that will identify markers of preclinical carcinogenesis. In-depth interviews are carried out using structured and semi-structured questionnaires. Sputum, blood and tumour specimens are collected and will be assessed for specific molecular markers ( e.g. genetic instability, mutation and expression profiling, and methylation status). Conclusions from The Liverpool Lung Project will be based around molecular-epidemiological and genotyping risk assessment models, as well as redefining the disease, and ultimately contributing to the development of new early lung cancer detection and treatment strategies.
Myeloablative megatherapy with autologous stem-cell rescue versus oral maintenance chemotherapy as consolidation treatment in patients with high-risk neuroblastoma: a randomised controlled trial
Authors: Frank Berthold, Joachim Boos, Stefan Burdach, Rudolf Erttmann, Günter Henze, Johann Hermann, Thomas Klingebiel, Bernhard Kremens, Freimut H Schilling, Martin Schrappe, Thorsten Simon, Barbara Hero
Journal: The Lancet Oncology (2005)
Overexpression of Cyclin D1 Promotes Tumor Cell Growth and Confers Resistance to Cisplatin-Mediated Apoptosis in an Elastase-<i>myc</i> Transgene–Expressing Pancreatic Tumor Cell Line
Authors: Hector Biliran, Yong Wang, Sanjeev Banerjee, Haiming Xu, Henry Heng, Archana Thakur, Aliccia Bollig, Fazlul H. Sarkar, Joshua D. Liao
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Elevated cyclin D1 in human pancreatic cancer correlates with poor prognosis. Because pancreatic cancer is invariably resistant to chemotherapy, the goal of this study was to examine whether the drug resistance of pancreatic cancer cells is in part attributed to cyclin D1 overexpression. Experimental Design: Stable overexpression and small interfering RNA (siRNA)–mediated knockdown of cyclin D1 were done in the newly established Ela-myc pancreatic tumor cell line. Cisplatin sensitivity of control, overexpressing, and siRNA-transfected cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, clonogenic, and apoptotic assays [DNA fragmentation, sub-G1, and poly(ADP-ribose) polymerase cleavage analysis]. The role of nuclear factor-κB and apoptotic proteins in cyclin D1-mediated chemoresistance was examined by EMSA and Western blotting, respectively. Results: Overexpression of cyclin D1 in Ela-myc pancreatic tumor cells promoted cell proliferation and anchorage-independent growth. Moreover, cyclin D1–overexpressing cells exhibited significantly reduced chemosensitivity and a higher survival rate upon cisplatin treatment, as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and clonogenic assays, respectively. Although overexpression of cyclin D1 rendered cells more resistant to cisplatin-induced apoptosis, siRNA-directed suppression of cyclin D1 expression resulted in enhanced susceptibility to cisplatin-mediated apoptosis. The attenuation of cisplatin-induced cell death in cyclin D1–overexpressing cells was correlated with the up-regulation of nuclear factor-κB activity and maintenance of bcl-2 and bcl-xl protein levels. Conclusions: These results suggest that overexpression of cyclin D1 can contribute to chemoresistance of pancreatic cancer cells because of the dual roles of cyclin D1 in promoting cell proliferation and in inhibiting drug-induced apoptosis.
Vitamin B<sub>6</sub>in the Treatment of Tardive Dyskinesia: A Double-Blind, Placebo-Controlled, Crossover Study
Authors: Vladimir Lerner, Chanoch Miodownik, Alexander Kaptsan, Hagit Cohen, Michael Matar, Uri Loewenthal, Moshe Kotler
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The authors' goal was to conduct a double-blind trial of vitamin B6 in the treatment of tardive dyskinesia in patients with schizophrenia. METHOD: Fifteen inpatients with schizophrenia who met research diagnostic criteria for tardive dyskinesia were randomly assigned to treatment with either vitamin B6 or placebo for 4 weeks in a double-blind crossover paradigm. The Extrapyramidal Symptom Rating Scale was used to assess patients weekly. RESULTS: Mean scores on the parkinsonism and dyskinetic movement subscales of the Extrapyramidal Symptom Rating Scale were significantly better in the third week of treatment with vitamin B6 than during the placebo period. CONCLUSIONS: Vitamin B6 appears to be effective in reducing symptoms of tardive dyskinesia.
Evidence based medicine
Authors: F. Davidoff, B. Haynes, D. Sackett, R. Smith
Journal: BMJ (1995)

Busy doctors have never had time to read all the journals in their disciplines. There are, for example, about 20 clinical journals in adult internal medicine that report studies of direct importance to clinical practice, and in 1992 these journals included over 6000 articles with abstracts: to keep up the dedicated doctor would need to read about 17 articles a day every day of the year.1 In earlier eras limitations in our understanding of human biology and the absence of powerful clinical research methods meant that major advances were published far less commonly than now. Consequently, clinicians' failure to keep up did not harm patients.

Not any more. Rapid advances in physics, chemistry, and molecular biology since the second world war have led to a huge increase in the possibilities for managing patients. Effective treatments have appeared often for the first time. In parallel with these scientific advances researchers have developed methods of applied research—epitomised by the randomised controlled trial—to identify which new ideas for diagnosis, treatment, and predicting outcome actually work. Many do not and may do more harm than good.

Doctors need to …
Estimating enrichment of repetitive elements from high-throughput sequence data
Authors: Daniel S Day, Lovelace J Luquette, Peter J Park, Peter V Kharchenko
Journal: Genome biology (2010)

We describe computational methods for analysis of repetitive elements from short-read sequencing data, and apply them to study histone modifications associated with the repetitive elements in human and mouse cells. Our results demonstrate that while accurate enrichment estimates can be obtained for individual repeat types and small sets of repeat instances, there are distinct combinatorial patterns of chromatin marks associated with major annotated repeat families, including H3K27me3/H3K9me3 differences among the endogenous retroviral element classes.
Factors associated with clinical deterioration shortly after PE
Authors: Christopher Kabrhel, Ikenna Okechukwu, Praveen Hariharan, James Kimo Takayesu, Peter MacMahon, Faris Haddad, Yuchiao Chang
Journal: Thorax (2014)

<h3>Background</h3> Several factors have been associated with mortality in the months after PE. Factors associated with short-term clinical deterioration or need for hospital-based intervention are less well known. <h3>Methods</h3> We prospectively enrolled consecutive emergency department patients with PE and recorded clinical, biomarker and radiographic data. We assessed hospitalised patients daily to identify clinical deterioration or need for hospital-based intervention for 5 days after PE. We captured postdischarge events via 5-day and 30-day interviews. We used univariate and multivariable models to assess associations with clinical deterioration, severe clinical deterioration and 30-day all-cause mortality. We also assessed the test characteristics of three published clinical decision rules. <h3>Results</h3> We enrolled 298 patients with PE: mean age 59 (SD±17) years; 152 (51%) male and 268 (90%) white race. 101 (34%) patients clinically deteriorated or required a hospital-based intervention within 5 days, and 197 (66%) did not. 27 (9%) patients suffered severe clinical deterioration and 12 died within 30 days. Factors independently associated with clinical deterioration were hypotension (p=0.001), hypoxia (p&lt;0.001), coronary disease (p=0.004), residual deep vein thrombosis (p=0.006) and right heart strain on echocardiogram (p&lt;0.001). In contrast, factors associated with 30-day all-cause mortality were active malignancy (p&lt;0.001) and congestive heart failure (p=0.009). The sensitivity of clinical decision rules was moderate (39–80%) for 5-day clinical deterioration but higher (67–100%) for 30-day mortality. <h3>Conclusions</h3> Most patients do not clinically deteriorate after PE diagnosis. Several factors are associated with short-term clinical deterioration, but these factors differ from those associated with 30-day mortality.
Proceedings of the ATS Workshop on Refractory Asthma
Authors: Sally E. Wenzel, John V. Fahy, Charles Irvin, Stephen P. Peters, Sheldon Spector, Stanley J. Szefler, Thomas B. Casale, Michelle M. Cloutier, Jack A. Elias, Mark C. Liu, Virginia Taggert
Journal: American Journal of Respiratory and Critical Care Medicine (2000)
Phase II Study to Evaluate the Efficacy and Safety of Neoadjuvant Lapatinib Plus Paclitaxel in Patients With Inflammatory Breast Cancer
Authors: Hamouda Boussen, Massimo Cristofanilli, Tal Zaks, Michelle DeSilvio, Vanessa Salazar, Neil Spector
Journal: Journal of Clinical Oncology (2010)

We conducted a phase II, open-label, multicenter study to evaluate the efficacy, safety, and tolerability of daily lapatinib plus weekly paclitaxel in treatment-naïve patients with inflammatory breast cancer (IBC).The primary end point was pathologic complete response (pCR). Secondary end points included combined clinical response rate (based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria and clinically evaluable skin disease criteria). Patients were assigned to either cohort A (human epidermal growth factor receptor 2 [HER2] 2+ or 3+ by immunohistochemistry [IHC] or fluorescent in situ hybridization [FISH] -amplified +/- epidermal growth factor receptor [EGFR] expression) or cohort B (HER2-negative/EGFR-positive). A subpopulation of cohort A considered HER2-positive by the current definition of overexpression (3+ by IHC or FISH-amplified) was also analyzed. Patients received lapatinib at 1,500 mg/d for 14 days, then lapatinib at 1,500 mg/d plus weekly paclitaxel (80 mg/m(2)) for 12 weeks, followed by surgical resection or additional chemotherapy.Forty-nine women were enrolled (cohort A, n = 42; cohort B, n = 7). Cohort B was terminated because of slow accrual and lack of efficacy observed in IBC patients with HER2-negative/EGFR-positive tumors enrolled onto the parallel study, EGF103009. pCR occurred in 18.2% (95% CI, 5.2% to 40.3%) of cohort A patients. Combined clinical response rate was 78.6% (95% CI, 63.2% to 89.7%) in all cohort A patients and 78.1% (95% CI, 60.0% to 90.7%) in the HER2-positive subset. Common adverse events included diarrhea, rash, alopecia, and nausea (> 50% of patients in both cohorts). The incidence of grade 3 diarrhea was 55%.Lapatinib monotherapy for 14 days followed by lapatinib plus paclitaxel for 12 weeks provided clinical benefit in IBC patients with HER2-overexpressing tumors without unexpected toxicity.
Abstract 5034: Both host and tumor cells group VIA phospholipase A2 are involved in ovarian cancer development, and lysophosphatidic acid restores the lost activities
Authors: Hui Li, Zhenwen Zhao, Gang Wei, Dongmei Wang, Hong Zhang, John Turk, Yan Xu
Journal: Cancer Research (2010)

Abstract Host-tumor cell interactions are recognized to be critical in tumor development. We have shown that group VIA phospholipase A2 (calcium-independent phospholipase A2beta, iPLA2β) is important in regulating extracellular lysophosphatidic acid (LPA) levels around human epithelial ovarian cancer (EOC) cells. To explore the role of iPLA2β in host-tumor cell interactions, we have used immunocompetent iPLA2β knockout (KO) mice and the mouse EOC cell line ID8. Tumorigenesis and ascites formation were reduced in iPLA2β-KO mice compared to wild type (WT) mice and were reduced further when ID8 cell iPLA2β levels were lowered with shRNA. LPA and lysophosphatidylcholine (LPC) levels in the tumor microenvironment were reduced in KO mice. LPA, but not LPC, restored ID8 cell migration, invasion, and colony formation with cells in which iPLA2β expression had been suppressed in vitro. LPA, but not LPC, also enhanced in vivo ascites formation and tumorigenesis in iPLA2β-KO mice. Autotaxin (ATX) activity in the tumor microenvironment correlated with tumor loading and was reduced in KO mice and enhanced by LPA in vivo. This is the first demonstration of a role for host cell iPLA2β in cancer, and these findings suggest that iPLA2β is a potential target for developing novel antineoplastic therapeutic strategies. 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 5034.
Increased Risk of Type 2 Diabetes From a Family History of Coronary Heart Disease and Type 2 Diabetes
Authors: Edwina H. Yeung, James S. Pankow, Brad C. Astor, Neil R. Powe, Christopher D. Saudek, W.H. Linda Kao
Journal: Diabetes Care (2006)

The “common soil” hypothesis (1) suggests that a family history of cardiovascular disease (CVD) increases the risk of type 2 diabetes through the common predispositions of obesity (2–7), hypertension (8), metabolic syndrome (9), and other pathways. While several studies (10–12) have shown that a family history of diabetes can increase cardiovascular risk, including subclinical atherosclerosis (11), no study has examined the converse, which is that familial risk of coronary heart disease (CHD) could influence the risk of type 2 diabetes. To test this hypothesis, we measured the association between the familial risk of CHD using the CHD family risk score (CHD-FRS) and incident type 2 diabetes in the Atherosclerosis Risk in Communities (ARIC) study.

The ARIC Study is a community-based study, which recruited individuals aged 45–64 years from four sites around the U.S. between 1987 and 1989 (13). Participants without diabetes were followed with three exams at ∼3-year intervals. Data collection methods have been previously recorded (14,15). This study analyzed data for 11,297 participants.

Family history of CHD was analyzed by the CHD-FRS. The CHD-FRS quantifies the composite risk for each participant based on observations of CHD in each family (excluding the participant) adjusted for the risk expected based on each family member’s age and sex with incidences found by the Framingham Heart Study (16). The CHD-FRS was analyzed both as a continuous and as a categorical variable with levels previously defined (14,15) as low (<0.5), moderate (−0.5 to 0.5), and high (≥0.5). A low CHD-FRS translates to having very few occurrences in older age or no occurrences of heart attacks at any age among the parents or siblings of the participant. A moderate CHD-FRS corresponds to a few occurrences of heart attacks among immediate family members. A …
AT1 receptor antagonist Candesartan in selected cirrhotic patients: Effect on portal pressure and liver fibrosis markers
Authors: Wilma Debernardi-Venon, Silvia Martini, Fiorella Biasi, Barbara Vizio, Angela Termine, Giuseppe Poli, Franco Brunello, Carlo Alessandria, Renato Bonardi, Giorgio Saracco, Mario Rizzetto, Alfredo Marzano
Journal: Journal of Hepatology (2007)
Detection of inspiratory flow limitation during sleep by computer assisted respiratory inductive plethysmography
Authors: V. Kaplan, J.N. Zhang, E.w Russi, K.e Bloch
Journal: European Respiratory Journal (2000)

The potential of respiratory inductive plethysmography (RIP) to detect inspiratory flow limitation during sleep was investigated. Sixteen sleep apnoea patients underwent polysomnography. Airflow by a flowmeter attached to a nasal mask, oesophageal and mask pressure were recorded along with calibrated RIP. Presence of inspiratory flow limitation was defined by constant or decreasing flow without pressure dependence throughout significant portions of inspiration, its absence by a linear or mildly alinear pressure:airflow relationship. Based on this standard, three of various computerized RIP derived parameters, with highest performance to detect flow limitation, were identified. They were combined to an inspiratory flow limitation, (IFL)-Index(RIP), which was validated prospectively in another 10 sleep apnoea patients. RIP derived fractional inspiratory time, peak to mean inspiratory flow ratio, and ribcage contribution to tidal volume had the highest accuracy to detect flow limitation (area under the receiver operating characteristic (ROC) curves 0.81, 0.76, 0.76, respectively, 160 comparisons). Prospective validation revealed an area under the ROC curve for the IFL-Index(RIP) to detect flow limitation of 0.89 (95% confidence interval 0.85 to 0.93, 200 comparisons) with sensitivity and specificity at the point of equality of 80%. It is concluded that inspiratory flow limitation may be assessed by computer assisted analysis of respiratory inductive plethysmography derived breathing patterns with clinically acceptable accuracy.
The Intracellular Life of<i>Cryptococcus neoformans</i>
Authors: Carolina Coelho, Anamelia L. Bocca, Arturo Casadevall
Journal: Annual Review of Pathology Mechanisms of Disease (2013)

Cryptococcus neoformans is a fungal pathogen with worldwide distribution. Serological studies of human populations show a high prevalence of human infection, which rarely progresses to disease in immunocompetent hosts. However, decreased host immunity places individuals at high risk for cryptococcal disease. The disease can result from acute infection or reactivation of latent infection, in which yeasts within granulomas and host macrophages emerge to cause disease. In this review, we summarize what is known about the cellular recognition, ingestion, and killing of C. neoformans and discuss the unique and remarkable features of its intracellular life, including the proposed mechanisms for fungal persistence and killing in phagocytic cells.
Oviduct-specific glycoprotein (OVGP1), a new serum biomarker for the detection of ovarian cancer
Authors: Sarah Maines-Bandiera, Michelle Woo, Laurie Molday, Martin Koebel, Marilyn Borugian, Peter Leung, Blake Gilks, Robert Molday, Nelly Auersperg
Journal: Cancer Research (2008)

4451  Ovarian carcinomas are the most lethal tumors of the female genital tract because most are detected late in the disease course. Our previous immunohistochemical study, using a polyclonal antibody, showed that oviduct-specific glycoprotein (OVGP1), normally a secreted and glycosylated protein of the oviduct, is aberrantly expressed and secreted in low grade ovarian epithelial neoplasias, suggesting that it may be detectable in the serum of women with such tumors. We generated a monoclonal antibody, clone OGP 7E10, to recombinant OVGP1, which recognizes the C-terminal region of the protein. It recognizes OVGP1 in conditioned medium at a molecular weight of 110-130 kDa and binds specifically to secretory epithelial cells of the mid- to late-proliferative phase oviduct. Immunohistochemical analysis of an ovarian tumor tissue array using OGP 7E10 demonstrated OVGP1 in 6/10 (60%) low grade serous carcinomas (LGSC), 168/185 (91%) high grade serous carcinomas (HGSC), 96/108 (89%) endometrioid carcinomas, 20/23 (87%) mucinous carcinomas and 102/116 (88%) clear cell carcinomas. Analysis with a Kaplan-Meier curve and log-rank statistics showed that positive OVGP1 staining in HGSCs was associated with a more favorable outcome (p
Antigen valence determines the binding of nominal antigen to cytolytic T cell clones.
Authors: R F Siliciano, R M Colello, A D Keegan, R Z Dintzis, H M Dintzis, H S Shin
Journal: The Journal of Experimental Medicine (1985)

We have shown that cytotoxic T cell clones specific for the nominal antigen FL will bind high molecular weight (600,000 to 2,000,000) polyacrylamide and Ficoll polymers conjugated with 200-600 FL groups per molecule. Low molecular weight polymers (40,000) with the same epitope density did not give stable binding. A high molecular weight polymer with a lower epitope density also failed to bind. Taken together, these results suggest that a substantial degree of multivalence is a necessary factor in the stable binding of nominal antigen to T cell clones.
Adjuvant Adenovirus-Mediated Delivery of Herpes Simplex Virus Thymidine Kinase Administration Improves Outcome of Liver Transplantation in Patients with Advanced Hepatocellular Carcinoma
Authors: Ning Li, Jianfeng Zhou, Danhui Weng, Chenghua Zhang, Lixin Li, Beibei Wang, Yang Song, Qiang He, Dongdong Lin, Dazhi Chen, Gang Chen, Qinglei Gao, Shixuan Wang, Gang Xu, Li Meng, YunPing Lu, Ding Ma
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Previous poor results of liver transplantation (LT) have been confirmed in patients with advanced hepatocellular carcinoma (HCC). Adenovirus-mediated delivery of herpes simplex virus thymidine kinase (ADV-TK) therapy is an established adjuvant treatment in cancer, and we evaluated its potential as an adjuvant treatment for HCC patients who underwent LT. Experimental Design: Forty-five HCC patients with tumors &amp;gt;5 cm in diameter participated in the study over a follow-up period of 50 months. Among these patients, 22 received LT only, and 23 received LT combined with ADV-TK therapy. All HCC patients enrolled in this study had tumors &amp;gt;5 cm in diameter and no metastasis in lungs or bones was detected by computed tomography or magnetic resonance imaging scans. Results: The recurrence-free survival and the overall survival in the LT plus ADV-TK therapy group were 43.5% and 69.6%, respectively, at 3 years; both values were significantly higher than those in the LT-only group (9.1% and 19.9%, respectively). In the nonvascular invasion subgroup, overall survival was 100% and recurrence-free survival was 83.3% in the patients receiving LT plus ADV-TK, significantly higher than the patients receiving LT only. Conclusions: HCC patients with no vascular invasion could be selected for LT followed by adjuvant ADV-TK therapy, regardless of intrahepatic huge or diffuse tumor. We propose that the current criteria for LT based on tumor size may be expanded if accompanied by ADV-TK therapy due to improved prognosis.