tbuckley/cabot-search huggingface dataset:
Testing the 'preliminary criteria for classification of SLE'.
Authors: J F Fries, R C Siegel
Journal: Annals of the Rheumatic Diseases (1973)

Systemic lupus erythematosus (SLE) is a disease with varied manifestations involving multiple organ systems, accompanied by multiple laboratory abnormalities, and characterized by exacerbations and remissions.Noting that 'uniform classification of defined groups of patients is necessary in order to assemble and compare data from different sources concerning natural history, evaluation of therapy, and epidemologic description', the Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association recently approached the formidable task of assembling criteria for the classi- fication of SLE (Cohen, Reynolds, Franklin, Kulka, Ropes, Shulman, and Wallace, 1971).To increase the utility of the criteria in population studies, the use of 'exclusions' and 'duration of manifestations' was avoided.A distinction between 'major' and 'minor' criteria was also not used.Thus, the form of these criteria differs from that of the Jones Criteria for Rheumatic Fever and the ARA Criteria for Rheuma- toid Arthritis (Arthritis Foundation, 1964).The committee collected a data base of 245 patients with unequivocal SLE, 234 patients with rheumatoid arthritis, and 217 patients with miscellaneous non- rheumatic diseases.Data was contributed by 52 investigators throughout the United States, who were requested to submit patients with 'unequivocal' SLE, and with 'classic' or 'definite' rheumatoid arthritis.Patients whose clinical course was atypical or in whom diagnostic uncertainty remained were excluded from these two groups.Data was sought on 74 variables of disease con- sidered of potential value for classification.Adequate data was obtained on 57 potential criteria, and the list was reduced to 21 by exclusion of variables which were least useful in distinguishing patients with 'SLE' from 'RA' and 'other' diseases.The final 21 variables were reduced to fourteen 'criteria' by grouping several variables within a single criterion (Table 1, overleaf).
TB or not TB: update from the ERS Respiratory Infection Assembly 10
Authors: M. Miravitlles, G. Ferrara, C. Lange, G. Dimopoulos, G. Rohde, F. Blasi, G.B. Migliori
Journal: European Respiratory Journal (2010)

Lower respiratory tract infections and tuberculosis represent some of the top health priorities in Europe. In the present report, the most recent advances in the field of disease control, clinical research and basic science of lower respiratory tract infections and tuberculosis are presented through analysis of some of the best abstracts presented at the 19th European Respiratory Society Congress in Vienna (Austria). Pathogenesis, diagnosis, treatment, prognostic factors and novel diagnostic techniques relevant for bacterial and viral infections, as well as new tools for the diagnosis of latent and active tuberculosis in different sub-groups of patients, are discussed. The growing epidemiological threat represented by multidrug-resistant and extensively drug-resistant tuberculosis cases is presented and its impact analysed.
Tumor antigens defined by cloned immunological probes are highly polymorphic and are not detected on autologous normal cells.
Authors: P L Ward, H Koeppen, T Hurteau, H Schreiber
Journal: The Journal of Experimental Medicine (1989)

We have isolated UV light-induced and spontaneous tumors along with nonmalignant cells and tissues from each host. CD8+ CTL clones generated to a number of highly immunogenic UV-induced tumors did not react with autologous normal fibroblasts nor with autologous second tumors. Using up to 25 independently induced tumors as targets, these CTL clones were found to be uniquely specific for the particular tumor used for immunization even when multiple tumors isolated from the same animals were used as targets. In addition to this extensive antigenic diversity of independently induced tumors, we found that a single cancer cell can express multiple independent antigens that were uniquely expressed on the tumor but were not detectable on autologous nonmalignant fibroblasts. A poorly immunogenic spontaneous tumor was also found to express an antigen that was uniquely specific for the immunizing tumor in that it was absent from any of 25 other tumors tested. This antigen was recognized by a mAb and not detected on autologous nonmalignant fibroblasts or on an autologous second spontaneous tumor. These findings demonstrate that syngeneic CTL clones or mAbs can define unique antigens on UV-induced or spontaneous tumors. The use of autologous nonmalignant fibroblast targets made it unlikely that these antigens were widely expressed on normal cells. The availability of cloned immunological probes to antigens on tumors isolated with autologous normal cells will allow a reliable identification of the genetic origins of unique antigens on experimentally induced and spontaneous tumors and permit a decisive answer to whether these unique antigens are encoded by normal genes or by genes that have undergone somatic mutations; i.e., whether these antigens are truly tumor specific.
Is Nuclear Factor κB an Attractive Therapeutic Target for Treating Cardiac Hypertrophy?
Authors: Nicole H. Purcell, Jeffery D. Molkentin
Journal: Circulation (2003)

ardiovascular disease is the leading cause of morbidity and mortality in the United States.In most instances, heart failure is the final consequence of many underlying disease etiologies such as long-standing hypertension, coronary heart disease, valvular insufficiency, arrhythmia, viral myocarditis, and mutations in sarcomereencoding genes.A compensatory enlargement of the myocardium, or hypertrophy, typically accompanies many of the predisposing insults discussed above and is a leading predictor for the development of more serious and life-threatening disease. 1,2Given the strong association between the presentation of pathological cardiac hypertrophy and a progressive deterioration in myocardial function, investigators have focused on understanding the molecular mechanisms that initiate the compensatory growth response or that precipitate the transition to heart failure.A number of signal transduction pathways are thought to play pivotal roles in mediating the hypertrophic growth of the myocardium in response to pathological stimuli. 3In this issue of Circulation, Cook et al 4 focus their attention on the nuclear factor (NF)-B signaling pathway as a potentially important intracellular mediator of cardiac hypertrophy.
miRNA-96 Suppresses KRAS and Functions as a Tumor Suppressor Gene in Pancreatic Cancer
Authors: Shuangni Yu, Zhaohui Lu, Changzheng Liu, Yunxiao Meng, Yihui Ma, Wugan Zhao, Jianping Liu, Jia Yu, Jie Chen
Journal: Cancer Research (2010)

Abstract Therapeutic applications of microRNA (miRNA) in KRAS-driven pancreatic cancers might be valuable, but few studies have explored this area. Here, we report that miR-96 directly targets the KRAS oncogene and functions as a tumor-suppressing miRNA in pancreatic cancer cells. Ectopic expression of miR-96 through a synthetic miRNA precursor inhibited KRAS, dampened Akt signaling, and triggered apoptosis in cells. In human clinical specimens, miR-96 was downregulated or deleted where an association with KRAS elevations was observed. In vitro and in vivo assays established that miR-96 decreased cancer cell invasion and migration and slowed tumor growth in a manner associated with KRAS downregulation. Our findings identify miR-96 as a potent regulator of KRAS, which may provide a novel therapeutic strategy for treatment of pancreatic cancer and other KRAS-driven cancers. Cancer Res; 70(14); 6015–25. ©2010 AACR.
The Duffy antigen/receptor for chemokines (DARC) is expressed in endothelial cells of Duffy negative individuals who lack the erythrocyte receptor.
Authors: S C Peiper, Z X Wang, K Neote, A W Martin, H J Showell, M J Conklyn, K Ogborne, T J Hadley, Z H Lu, J Hesselgesser, R Horuk
Journal: The Journal of Experimental Medicine (1995)

The Duffy antigen/receptor for chemokines (DARC), first identified on erythrocytes, functions not only as a promiscuous chemokine receptor but also as a receptor for the malarial parasite, Plasmodium vivax. The recent finding that DARC is ubiquitously expressed by endothelial cells lining postcapillary venules provides a possible insight into the function of this receptor because this anatomic site is an active interface for leukocyte trafficking. However, the biological significance of DARC is questionable since it has not yet been determined whether individuals lacking the expression of this protein on their erythrocytes (Duffy negative individuals), who are apparently immunologically normal, express the receptor on endothelial cells. However, we report here that DARC is indeed expressed in endothelial cells lining postcapillary venules and splenic sinusoids in individuals who lack the erythrocyte receptor. These findings are based on immunohistochemical, biochemical, and molecular biological analysis of tissues from Duffy negative individuals. We also present data showing that, in contrast to erythrocyte DARC, cells transfected with DARC internalize radiolabeled ligand. We conclude that the DARC may play a critical role in mediating the effects of proinflammatory chemokines on the interactions between leukocyte and endothelial cells since the molecular pathology of the Duffy negative genotype maintains expression on the latter cell type.
Population genomics of human gene expression
Authors: Barbara E Stranger, Alexandra C Nica, Matthew S Forrest, Antigone Dimas, Christine P Bird, Claude Beazley, Catherine E Ingle, Mark Dunning, Paul Flicek, Daphne Koller, Stephen Montgomery, Simon Tavaré, Panos Deloukas, Emmanouil T Dermitzakis
Journal: Nature Genetics (2007)
Novel therapeutic approaches to post-infarction remodelling
Authors: D. Fraccarollo, P. Galuppo, J. Bauersachs
Journal: Cardiovascular Research (2012)

Adverse cardiac remodelling is a major cause of morbidity and mortality following acute myocardial infarction (MI). Mechanical and neurohumoral factors involved in structural and molecular post-infarction remodelling were important targets in research and treatment for years. More recently, therapeutic strategies that address myocardial regeneration and pathophysiological mechanisms of infarct wound healing appear to be useful novel tools to prevent progressive ventricular dilation, functional deterioration, life-threatening arrhythmia, and heart failure. This review provides an overview of future and emerging therapies for cardiac wound healing and remodelling after MI.
Comparison of the effect of terlipressin and albumin on arterial blood volume in patients with cirrhosis and tense ascites treated by paracentesis: a randomised pilot study
Authors: R Moreau
Journal: Gut (2002)

Patients with cirrhosis and tense ascites treated by paracentesis alone have a decrease in effective arterial blood volume after ascites removal. Although intravenous albumin is effective in preventing paracentesis induced decreased arterial blood volume, its clinical use is controversial. As paracentesis induces arteriolar vasodilation which plays a role in the development of decreased effective arterial blood volume, administration of a vasoconstrictor (terlipressin) could prevent circulatory alterations due to paracentesis.To perform a pilot study comparing the effects of terlipressin and albumin on effective arterial blood volume in patients with cirrhosis treated by paracentesis for tense ascites.Twenty patients with cirrhosis and tense ascites were randomly assigned to be treated by either paracentesis and terlipressin or paracentesis and albumin. Terlipressin (3 mg) or albumin (8 g/l of removed ascites) were administered on the day of paracentesis. Effective arterial blood volume was assessed by measuring plasma renin concentrations at baseline and on the day of hospital discharge (4-6 days after treatment). Decreased effective arterial blood volume was defined as an increase in plasma renin concentrations on the day of hospital discharge of more than 50% of baseline values.Irrespective of the treatment group, mean values for plasma renin concentrations at hospital discharge did not differ from their respective baseline values (p=0.10). Baseline plasma levels of renin concentrations did not differ between the terlipressin and albumin groups (p=0.61). Changes from baseline in plasma renin concentrations did not differ between groups (p=0.39). Three patients in the terlipressin group and three in the albumin group developed decreased arterial blood volume.This randomised pilot study suggests that terlipressin may be as effective as intravenous albumin in preventing a decrease in effective arterial blood volume in patients with cirrhosis treated by paracentesis for tense ascites.
Three-Arm Randomized Study of Two Cisplatin-Based Regimens and Paclitaxel Plus Gemcitabine in Advanced Non–Small-Cell Lung Cancer: A Phase III Trial of the European Organization for Research and Treatment of Cancer Lung Cancer Group—EORTC 08975
Authors: Egbert F. Smit, Jan P.A.M. van Meerbeeck, Pilar Lianes, Channa Debruyne, Catherine Legrand, Franz Schramel, Hans Smit, Rabab Gaafar, Bonne Biesma, Chris Manegold, Niels Neymark, Giuseppe Giaccone
Journal: Journal of Clinical Oncology (2003)

To compare the therapeutic efficacy of paclitaxel plus cisplatin (arm A) versus gemcitabine plus cisplatin (arm B) and arm A versus paclitaxel plus gemcitabine (arm C) in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC).Patients were randomly assigned to receive either paclitaxel 175 mg/m2 (3-hour infusion, day 1) or gemcitabine 1,250 mg/m2 (days 1 and 8) both combined with cisplatin 80 mg/m2 (day 1) or paclitaxel 175 mg/m2 (3-hour infusion, day 1) combined with gemcitabine 1,250 mg/m2 (days 1 and 8). Primary end point was comparison of overall survival for B versus A and C versus A. Secondary end points included response rate and duration, progression-free survival, toxicities, quality of life [QoL], and cost of treatment.Four hundred eighty patients (arm A, 159; arm B, 160; arm C, 161 patients) were enrolled; all baseline characteristics were balanced. Median survival times were as follows: arm A, 8.1 months; arm B, 8.9 months; arm C, 6.7 months. Response rates were 31.8% for arm A, 36.6% for arm B, and 27.7% for arm C. Other than myelosuppression (B v A, P <.005), no statistically or clinically significant differences were observed for secondary end points. The average treatment costs were 25% higher in arm C as compared with arms A and B.Gemcitabine plus cisplatin and paclitaxel plus gemcitabine do not increase overall survival in patients with advanced NSCLC as compared with paclitaxel plus cisplatin. Treatment was well tolerated, and most QoL parameters were similar, but costs associated with the nonplatinum arm were highest.
European hospital adherence to GOLD recommendations for chronic obstructive pulmonary disease (COPD) exacerbation admissions: Table 1
Authors: C Michael Roberts, Jose Luis Lopez-Campos, Francisco Pozo-Rodriguez, Sylvia Hartl
Journal: Thorax (2013)

Understanding how European care of chronic obstructive pulmonary disease (COPD) admissions vary against guideline standards provides an opportunity to target appropriate quality improvement interventions. In 2010–2011 an audit of care against the 2010 'Global initiative for chronic Obstructive Lung Disease' (GOLD) standards was performed in 16 018 patients from 384 hospitals in 13 countries. Clinicians prospectively identified consecutive COPD admissions over a period of 8 weeks, recording clinical care measures on a web-based data tool. Data were analysed comparing adherence to 10 key management recommendations. Adherence varied between hospitals and across countries. The lack of available spirometry results and variable use of oxygen and non-invasive ventilation (NIV) are high impact areas identified for improvement.
Bone marrow transplants do not help in breast cancer
Authors: b. S. Gottlieb
Journal: BMJ (1999)

Preliminary results released early from four ongoing clinical studies of breast cancer treatments indicate that high dose chemotherapy followed by bone marrow transplantation may not significantly improve survival, although positive results from a fifth trial, also released early, seem to suggest otherwise.

For almost a decade, ultra high doses of chemotherapy followed by a bone marrow transplant to rescue the destruction of the immune …
Ginkgo biloba extract 761 reduces doxorubicin-induced apoptotic damage in rat hearts and neonatal cardiomyocytes
Authors: T.-J. Liu, Y.-C. Yeh, C.-T. Ting, W.-L. Lee, L.-C. Wang, H.-W. Lee, K.-Y. Wang, H.-C. Lai, H.-C. Lai
Journal: Cardiovascular Research (2008)

AimsThe objective of this study was to investigate whether a cytoprotective herb-derived agent, Ginkgo biloba extract (EGb) 761, could have a beneficial effect on doxorubicin-induced cardiac toxicity in vitro and in vivo.
Parental Depression: Animal Models of an Adverse Life Event
Authors: D. Jeffrey Newport, Zachary N. Stowe, Charles B. Nemeroff
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: This article reviews findings in preclinical research on the adverse impact of parental depression on the development of offspring, with emphasis on the relevance of this research for the psychiatric care of depressed parents. METHOD: The authors reviewed literature from the last 40 years reporting laboratory animal studies pertaining to the persistent effects of parental stress and parenting deficits on neurobehavioral and neurobiological development in offspring. RESULTS: Animal studies indicate that disrupted parenting produces a persistent, deleterious biobehavioral impact on offspring. Stressors, including maternal separation, variable foraging, and a variety of prenatal maternal challenges, produce offspring behaviors reminiscent of the cardinal features of anxiety and affective disorders. The stress paradigms also uniformly produce persistent hyperresponsivity in hypothalamic-pituitary-adrenal axis activity secondary to hypersecretion of corticotropin-releasing hormone. These findings bear striking similarities to findings for stress-related illnesses in humans, including major depression. CONCLUSIONS: Data from research on animal parenting reinforce the idea that parental mental illness may pose the first adverse life event for a child. A thorough risk-benefit assessment for the psychiatric care of parents of young children must consider the impact on the infant of exposure both to treatment and to parental illness. Preclinical data regarding the risk to offspring posed by untreated parental mental illness should be incorporated into clinical decision making in the treatment of parents with mental illness.
Screening Mammography in Older Women
Authors: Louise C. Walter, Mara A. Schonberg
Journal: JAMA (2014)

Guidelines recommend individualizing screening mammography decisions for women aged 75 years and older. However, little pragmatic guidance is available to help counsel patients.To provide an evidence-based approach for individualizing decision-making about screening mammography in older women.We searched PubMed for English-language studies in peer-reviewed journals published from January 1, 1990, to February 1, 2014, to identify risk factors for late-life breast cancer in women aged 65 years and older and to quantify the benefits and harms of screening mammography for women aged 75 years and older.Age is the major risk factor for developing and dying from breast cancer. Breast cancer risk factors that reflect hormonal exposures in the distant past, such as age at first birth or age at menarche, are less predictive of late-life breast cancer than factors indicating recent hormonal exposures such as high bone mass or obesity. Randomized trials of the benefits of screening mammography did not include women older than 74 years. Thus it is not known if screening mammography benefits older women. Observational studies favor extending screening mammography to older women who have a life expectancy of more than 10 years. Modeling studies estimate 2 fewer breast cancer deaths/1000 women who in their 70s continue biennial screening for 10 years instead of stopping screening at age 69. Potential harms of continued screening over 10 years include false-positive mammograms in approximately 200/1000 women screened and overdiagnosis (ie, finding breast cancer that would not have clinically surfaced otherwise) in approximately 13/1000 women screened. Providing information about life expectancy along with potential benefits and harms of screening may help older women's decision-making about screening mammography.For women with less than a 10-year life expectancy, recommendations to stop screening mammography should emphasize increased potential harms from screening and highlight health promotion measures likely to be beneficial over the short term. For women with a life expectancy of more than 10 years, deciding whether potential benefits of screening outweigh harms becomes a value judgment for patients, requiring a realistic understanding of screening outcomes.
GENDER DIFFERENCES IN CARDIOVASCULAR RISK IN DIABETIC AND NON-DIABETIC OUTPATIENTS AT RISK OF OR WITH ATHEROTHROMBOSIS IN THE REACH REGISTRY
Authors: Jacob A. Udell, Annie Nguyen, Philippe Steg, Benjamin Scirica, Kim Eagle, Erik Ohman, Shinya Goto, Kevin Crowley, Peter Wilson, Deepak Bhatt
Journal: Journal of the American College of Cardiology (2012)
Aberrant L1 Cell Adhesion Molecule Affects Tumor Behavior and Chemosensitivity in Anaplastic Thyroid Carcinoma
Authors: Koon Soon Kim, Jeong-Ki Min, Zhe Long Liang, Kyungmin Lee, Jung Uee Lee, Kwang-Hee Bae, Min Hee Lee, Seong Eun Lee, Min Jeong Ryu, Soung Jung Kim, Yong Kyoung Kim, Min Jeong Choi, Young Suk Jo, Jin-Man Kim, Minho Shong
Journal: Clinical Cancer Research (2012)

Anaplastic thyroid carcinoma (ATC) is one of the most invasive human cancers and has a poor prognosis. Molecular targets of ATC that determine its highly aggressive nature remain unidentified. This study investigated L1 cell adhesion molecule (L1CAM) expression and its role in tumorigenesis of ATCs.Expression of L1CAM in thyroid cancer was evaluated by immunohistochemical analyses of tumor samples from patients with thyroid cancer. We investigated the role of L1CAM in proliferation, migration, invasion, and chemoresistance using short hairpin RNA (shRNA) knockdown experiments in human ATC cell lines. Finally, we evaluated the role of L1CAM on tumorigenesis with ATC xenograft assay in a nude mouse model.L1CAM expression was not detectable in normal follicular epithelial cells of the thyroid or in differentiated thyroid carcinoma. In contrast, analysis of ATC samples showed specifically higher expression of L1CAM in the invasive area of the tumor. Specific knockdown of L1CAM in the ATC cell lines, FRO and 8505C, caused a significant decrease in the proliferative, migratory, and invasive capabilities of the cells. Suppression of L1CAM expression in ATC cell lines increased chemosensitivity to gemcitabine or paclitaxel. Finally, in an ATC xenograft model, depletion of L1CAM markedly reduced tumor growth and increased the survival of tumor-bearing mice.We report that L1CAM is highly expressed in the samples taken from patients with ATCs. L1CAM plays an important role in determining tumor behavior and chemosensitivity in cell lines derived from ATCs. Therefore, we suggest that L1CAM may be an important therapeutic target in patients with ATCs.