tbuckley/cabot-search huggingface dataset:
Prognostic and Predictive Value of a Malignancy-Risk Gene Signature in Early-Stage Non–Small Cell Lung Cancer
Authors: Dung-Tsa Chen, Ying-Lin Hsu, William J. Fulp, Domenico Coppola, Eric B. Haura, Timothy J. Yeatman, W. Douglas Cress
Journal: JNCI Journal of the National Cancer Institute (2011)

The malignancy-risk gene signature is composed of numerous proliferative genes and has been applied to predict breast cancer risk. We hypothesized that the malignancy-risk gene signature has prognostic and predictive value for early-stage non–small cell lung cancer (NSCLC) patients. The ability of the malignancy-risk gene signature to predict overall survival (OS) of early-stage NSCLC patients was tested using a large NSCLC microarray dataset from the Director's Challenge Consortium (n = 442) and two independent NSCLC microarray datasets (n = 117 and 133, for the GSE13213 and GSE14814 datasets, respectively). An overall malignancy-risk score was generated by principal component analysis to determine the prognostic and predictive value of the signature. An interaction model was used to investigate a statistically significant interaction between adjuvant chemotherapy (ACT) and the gene signature. All statistical tests were two-sided. The malignancy-risk gene signature was statistically significantly associated with OS (P < .001) of NSCLC patients. Validation with the two independent datasets demonstrated that the malignancy-risk score had prognostic and predictive values: Of patients who did not receive ACT, those with a low malignancy-risk score had increased OS compared with a high malignancy-risk score (P = .007 and .01 for the GSE13212 and GSE14814 datasets, respectively), indicating a prognostic value; and in the GSE14814 dataset, patients receiving ACT survived longer in the high malignancy-risk score group (P = .03), and a statistically significant interaction between ACT and the signature was observed (P = .02). The malignancy-risk gene signature was associated with OS and was a prognostic and predictive indicator. The malignancy-risk gene signature could be useful to improve prediction of OS and to identify those NSCLC patients who will benefit from ACT.
Public Knowledge of Benefits of Breast and Prostate Cancer Screening in Europe
Authors: G. Gigerenzer, J. Mata, R. Frank
Journal: JNCI Journal of the National Cancer Institute (2009)

Making informed decisions about breast and prostate cancer screening requires knowledge of its benefits. However, country-specific information on public knowledge of the benefits of screening is lacking. Face-to-face computer-assisted personal interviews were conducted with 10 228 persons selected by a representative quota method in nine European countries (Austria, France, Germany, Italy, the Netherlands, Poland, Russia, Spain, and the United Kingdom) to assess perceptions of cancer-specific mortality reduction associated with mammography and prostate-specific antigen (PSA) screening. Participants were also queried on the extent to which they consulted 14 different sources of health information. Correlation coefficients between frequency of use of particular sources and the accuracy of estimates of screening benefit were calculated. Ninety-two percent of women overestimated the mortality reduction from mammography screening by at least one order of magnitude or reported that they did not know. Eighty-nine percent of men overestimated the benefits of PSA screening by a similar extent or did not know. Women and men aged 50–69 years, and thus targeted by screening programs, were not substantially better informed about the benefits of mammography and PSA screening, respectively, than men and women overall. Frequent consulting of physicians ( r = .07, 95% confidence interval [CI] = 0.05 to 0.09) and health pamphlets ( r = .06, 95% CI = 0.04 to 0.08) tended to increase rather than reduce overestimation. The vast majority of citizens in nine European countries systematically overestimate the benefits of mammography and PSA screening. In the countries investigated, physicians and other information sources appear to have little impact on improving citizens’ perceptions of these benefits.
CD4 Effector T Cell Subsets in the Response to Influenza
Authors: Eulogia Román, Ellen Miller, Allen Harmsen, James Wiley, Ulrich H. von Andrian, Gail Huston, Susan L. Swain
Journal: The Journal of Experimental Medicine (2002)

The immune response of naive CD4 T cells to influenza virus is initiated in the draining lymph nodes and spleen, and only after effectors are generated do antigen-specific cells migrate to the lung which is the site of infection. The effector cells generated in secondary organs appear as multiple subsets which are a heterogeneous continuum of cells in terms of number of cell divisions, phenotype and function. The effector cells that migrate to the lung constitute the more differentiated of the total responding population, characterized by many cell divisions, loss of CD62L, down-regulation of CCR7, stable expression of CD44 and CD49d, and transient expression of CCR5 and CD25. These cells also secrete high levels of interferon γ and reduced levels of interleukin 2 relative to those in the secondary lymphoid organs. The response declines rapidly in parallel with viral clearance, but a spectrum of resting cell subsets reflecting the pattern at the peak of response is retained, suggesting that heterogeneous effector populations may give rise to corresponding memory populations. These results reveal a complex response, not an all-or-none one, which results in multiple effector phenotypes and implies that effector cells and the memory cells derived from them can display a broad spectrum of functional potentials.
Peroneal tendon subluxation: the other lateral ankle injury
Authors: Jennifer A Roth, Walter C Taylor, Joseph Whalen
Journal: British Journal of Sports Medicine (2009)

Ankle injuries are a frequent cause of patient visits to the emergency department and orthopaedic and primary care offices. Although lateral ligament sprains are the most common pathologic conditions, peroneal tendon subluxations occur with a similar inversion mechanism. Multiple grades of subluxation have been described with a recent addition of intrasheath subluxation. Magnetic resonance imaging is the best imaging modality to view the peroneal tendons at the retrofibular groove. Currently, point-of-care ultrasound is gaining clinical ground, especially for the dynamic viewing capability to capture an episodic subluxation. Although conservative treatment may be attempted for an acute injury, it has a low rate of success for the prevention of recurrent subluxation. Surgical procedures of various techniques have resulted in excellent recovery rates and faster return to play. The aim of this paper was to give a complete review of the current literature on peroneal tendon subluxation and to propose a clinical algorithm to help guide diagnosis and treatment. The goal of this study was to heighten clinical awareness to improve earlier detection and treatment of this sometimes elusive diagnosis.
GLI2 Knockdown Using an Antisense Oligonucleotide Induces Apoptosis and Chemosensitizes Cells to Paclitaxel in Androgen-Independent Prostate Cancer
Authors: Shintaro Narita, Alan So, Susan Ettinger, Norihiro Hayashi, Mototsugu Muramaki, Ladan Fazli, Youngsoo Kim, Martin E. Gleave
Journal: Clinical Cancer Research (2008)

Abstract Purpose: GLI transcription factors mediate hedgehog signaling and have been implicated in several human malignancies, including prostate cancer. The objectives of this study were to characterize GLI2 expression levels in human prostate cancer cell lines and tissues to test the effect of antisense oligonucleotide (ASO) targeting GLI2 on androgen-independent (AI) prostate cancer cell lines. Experimental Design: A tissue microarray was used to characterize differences in GLI2 expression in benign prostate hyperplasia, prostate cancer treated by neoadjuvant hormonal therapy and AI prostate cancer. The effects of GLI2 ASO on PC-3 cell growth and paclitaxel chemosensitivity were assessed in vitro and in vivo. Oligonucleotide spotted microarray analysis was used to determine alteration in GLI2 coregulated genes after ASO treatment. Results: The expression of GLI2 was significantly higher in prostate cancer than in benign prostate hyperplasia, decreased after androgen ablation in a time-dependent fashion, but became highly expressed again in AI prostate cancer. GLI2 ASO treatment of PC-3 cells reduced GLI2 mRNA and protein levels in a dose-dependent manner. GLI2 knockdown increased PC-3 cell apoptotic rates and significantly decreased cell growth and modulated levels of apoptosis-related genes, such as Bcl2, Bcl-xL, and clusterin. GLI2 knockdown also changed levels of several cell cycle regulators, such as cyclin D1, p27, and PKC-η. Systematic administration of GLI2 ASO in athymic mice significantly delayed PC-3 tumor progression and enhanced paclitaxel chemosensitivity. Conclusions: These findings suggest that increased levels of GLI2 correlates with AI progression and that GLI2 may be a therapeutic target in castrate-resistant prostate cancer.
Oats induced villous atrophy in coeliac disease
Authors: K E A Lundin
Journal: Gut (2003)

The current trend is to allow coeliac disease (CD) patients to introduce oats to their gluten free diet. We sought further data from the clinical setting with regards to oats consumption by coeliac patients. Several oat products were tested for wheat contamination using a commercial enzyme linked immunoassay (ELISA) kit, and six samples were examined by an ELISA using a cocktail of monoclonal antibodies, mass spectrometry, and western blot analysis. Nineteen adult CD patients on a gluten free diet were challenged with 50 g of oats per day for 12 weeks. Serological testing and gastroduodenoscopy was performed before and after the challenge. Biopsies were scored histologically and levels of mRNA specific for interferon γ were determined by reverse transcription-polymerase chain reaction analysis. Oats were well tolerated by most patients but several reported initial abdominal discomfort and bloating. One of the patients developed partial villous atrophy and a rash during the first oats challenge. She subsequently improved on an oats free diet but developed subtotal villous atrophy and dramatic dermatitis during a second challenge. Five of the patients showed positive levels of interferon γ mRNA after challenge. Some concerns therefore remain with respect to the safety of oats for coeliacs.
A major sporting event does not necessarily mean an increased workload for accident and emergency departments. Euro96 Group of Accident and Emergency Departments.
Authors: M W Cooke, T F Allan, S Wilson
Journal: British Journal of Sports Medicine (1999)

To determine whether there were any changes in attendance at accident and emergency departments that could be related to international football matches (Euro96 tournament).Fourteen accident and emergency departments (seven adjacent to and seven distant from a Euro96 venue) provided their daily attendance figures for a nine week period: three weeks before, during, and after the tournament. The relation between daily attendance rates and Euro96 football matches was assessed using a generalised linear model and analysis of variance. The model took into account underlying trends in attendance rates including day of the week.The 14 hospitals contributed 172 366 attendances (mean number of daily attendances 195). No association was shown between the number of attendances at accident and emergency departments and the day of the football match, whether the departments were near to or distant from stadia or the occurrence of a home nation match. The only observed independent predictors of variation were day of the week and week of the year. Attendance rates were significantly higher on Sunday and/or Monday; Monday was about 9% busier than the daily average. Increasing attendance was observed over time for 86% of the hospitals.Large sports tournaments do not increase the number of patients attending accident and emergency departments. Special measures are not required for major sporting events over and above the capacity of an accident and emergency department to increase its throughput on other days.
P1291 EFFECTIVENESS OF HBV RAPID TESTS IN INVOLVEMENT OF CARE. RESULTS OF A RANDOMIZED, MULTICENTER STUDY
Authors: J. Bottero, A. Boyd, J. Gozlan, F. Carrat, A. Collignon, N. Boo, P. Dhotte, B. Varsat, C. Charlois, O. Cha, P. Campa, P.-M. Girard, K. Lacombe
Journal: Journal of Hepatology (2014)
Sudden cardiac death in young people with apparently normal heart
Authors: D Corrado
Journal: Cardiovascular Research (2001)

Objective: The aim of the present study was to assess the prevalence of subtle morphologic substrates, clinically unrecognizable, underlying sudden cardiac death (SCD) in young people with apparently normal heart. Methods: In the time interval 1979–1998, 273 consecutive cases of SCD in young people (≤35 years) which occurred in the Veneto Region of Italy were prospectively studied. Following exclusion of extracardiac causes of sudden death, the heart was examined according to a detailed morphologic protocol consisting of macroscopic and histologic examination, including study of the specialized conduction system by serial sections. Results: At macroscopic examination, 197 SCD victims (72%) had an overt underlying structural heart disease such as cardiomyopathy in 56, obstructive coronary atherosclerosis in 54, valve disease in 32, non-atherosclerotic coronary artery disease in 28, aortic rupture in 13, postoperative congenital heart disease in five, and other disease in nine. The remaining 76 cases (28%) (50 males and 26 females, aged 4–35 years, mean 23±5 years) had a macroscopically normal heart. A total of 28 of them (37%) had experienced one or more of the following prodroma: syncope, palpitations or both in 20, ECG abnormalities in 18 and arrhythmias in ten. In 79% of them, histologic examination disclosed concealed pathologic substrates consisting of focal myocarditis in 27 cases, regional arrhythmogenic right ventricular cardiomyopathy, mostly localized to RV outflow tract, in nine, and conduction system abnormalities in 24 (leading to ventricular preexcitation in 18 and heart block in six). In 16 hearts (6%) there was no evidence of structural heart disease even after histologic study. Conclusion: Macroscopic heart features were normal in nearly one-third of young SCD victims. In 79% of them, however, histologic study unmasked concealed pathologic substrates such as focal myocarditis or cardiomyopathy and conduction system diseases. A total of 16 victims (6%) had no evidence of structural heart disease and the mechanism of their SCD remained unexplained.
Cardiovascular Disease Risk Prediction With and Without Knowledge of Genetic Variation at Chromosome 9p21.3
Authors: Nina P. Paynter
Journal: Annals of Internal Medicine (2009)

Although genetic variation at chromosome 9p21.3 is associated with incident cardiovascular disease, it is unclear whether screening for this polymorphism improves risk prediction.To determine whether knowledge of variation at chromosome 9p21.3 provides predictive information beyond that from other readily available risk factors.Prospective cohort study.United States.22 129 female white health professionals participating in the Women's Genome Health Study, initially without any major chronic disease, who were prospectively followed over a median of 10.2 years for incident cardiovascular disease.Polymorphism at rs10757274 in chromosome 9p21.3 and additional cardiovascular disease risk factors (blood pressure, smoking status, diabetes, blood levels of cholesterol, high-sensitivity C-reactive protein, and family history of premature myocardial infarction).Polymorphism at rs10757274 was associated with an adjusted hazard ratio for incident cardiovascular disease of 1.25 (95% CI, 1.04 to 1.51) for the AG genotype and 1.32 (CI, 1.07 to 1.63) for the GG genotype. However, the addition of the genotype to a prediction model based on traditional risk factors, high-sensitivity C-reactive protein, and family history of premature myocardial infarction had no effect on model discrimination as measured by the c-index (0.807 to 0.809) and did not improve the Net Reclassification Improvement score (-0.2%; P = 0.59) or the Integrated Discrimination Improvement score (0.0; P = 0.18).Study participants were all white women.In this large prospective cohort of white women, genetic variation in chromosome 9p21.3 was associated with incident cardiovascular disease but did not improve on the discrimination or classification of predicted risk achieved with traditional risk factors, high-sensitivity C-reactive protein, and family history of premature myocardial infarction.
Response to Letter Regarding Article, “Peripartum Cardiomyopathy as a Part of Familial Dilated Cardiomyopathy”
Authors: Karin Y. van Spaendonck-Zwarts, J. Peter van Tintelen, Jan D.H. Jongbloed, Dirk J. van Veldhuisen, Rik van der Werf, Maarten P. van den Berg, Walter J. Paulus, Dennis Dooijes
Journal: Circulation (2011)
Glucagon
Authors: BENEDICT R. LUCCHESI, DAVID R. STUTZ, ROBERT A. WINFIELD, JEANNE L. BROWN, NANCY L. NOBEL
Journal: Circulation Research (1969)

The effects of glucagon on atrioventricular nodal automaticity and ventricular automaticity were studied in anesthetized open-chest dogs. After the sinoatrial node was crushed, glucagon, 4 µg/kg, produced a marked and sustained increase in the rate of A-V nodal discharge (27.6 ± 10.1 vs. 117.4 ± 6.5 beats/min) that persisted for an average of 20 minutes. The effect of glucagon was not modified by previous administration of propranolol, 2 mg/kg. Repeated administrations of glucagon, 1 µg/kg every 15 min, for a period of 2 hours, sustained A-V nodal rhythm. The effects of glucagon on ventricular automaticity were studied in unanesthetized dogs 48 and 72 hours after surgical ligation of the anterior descending coronary artery and were compared to the effects of epinephrine. Unlike the catecholamine, glucagon did not enhance ventricular automaticity in the infarcted myocardium. The results suggest that glucagon might be of therapeutic value in the management of heart block and in cardiogenic shock after acute myocardial infarction. The inability to augment ventricular ectopic activity suggests that glucagon possesses an advantage over the catecholamines as an inotropic agent.
Unmasking of Brugada Syndrome by Lithium
Authors: Dawood Darbar, Tao Yang, Keith Churchwell, Arthur A.M. Wilde, Dan M. Roden
Journal: Circulation (2005)

The characteristic ECG pattern of ST-segment elevation in V1 and V2 in the Brugada syndrome is dynamic; it is often intermittently present in affected individuals and can be unmasked by sodium channel blockers, including antiarrhythmic drugs and tricyclic antidepressants. We report here 2 patients who developed the Brugada ECG pattern after administration of lithium, a commonly used drug not previously reported to block cardiac sodium channels.Lithium induced transient ST-segment elevation (type 1 Brugada pattern) in right precordial leads at therapeutic concentrations in 2 patients with bipolar disorder. Lithium withdrawal in the patients resulted in reversion to type 2 or 3 Brugada patterns or resolution of ST-T abnormalities. In Chinese hamster ovary cells transfected with SCN5A, which encodes the cardiac sodium channel, lithium chloride caused concentration-dependent block of peak INa at levels well below the therapeutic range (IC50 of 6.8+/-0.4 micromol/L).The widely used drug lithium is a potent blocker of cardiac sodium channels and may unmask patients with the Brugada syndrome.
Induction of Apoptosis by Flavopiridol in Human Neuroblastoma Cells Is Enhanced under Hypoxia and Associated With <b> <i>N-myc</i> </b> Proto-oncogene Down-Regulation
Authors: Maura Puppo, Sandra Pastorino, Giovanni Melillo, Annalisa Pezzolo, Luigi Varesio, Maria Carla Bosco
Journal: Clinical Cancer Research (2004)

Neuroblastoma is the most common extracranial solid tumor of children that arises from the sympathetic nervous system. Survival rates for neuroblastoma patients is low despite intensive therapeutic intervention, and the identification of new effective drugs remains a primary goal. The cyclin-dependent kinase inhibitor, flavopiridol, has demonstrated growth-inhibitory and cytotoxic activity against various tumor types. Our aim was to investigate flavopiridol effects on advanced-stage, N-myc proto-oncogene (MYCN)-amplified human neuroblastomas and the modulation of its activity by hypoxia, a critical determinant of tumor progression and a major challenge of therapy.Cell viability was monitored by 3-(4,5 dimethyl-2 thiazolyl)-2,5 diphenyl-2H tetrazolium bromide (MTT) and trypan blue dye exclusion assays; DNA synthesis was assessed with the bromodeoxyuridine pulse-labeling technique; apoptosis was studied by Giemsa staining, DNA fragmentation, terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling reaction, flow cytometric determination of hypodiploid DNA content, and evaluation of caspase activity and cytochrome c (CytC) release; MYCN expression was determined by Northern and Western blotting.Flavopiridol caused dose- and time-dependent decreases in neuroblastoma viability by inducing apoptosis, as confirmed by morphologic and biochemical criteria. Cell death was preceded by DNA synthesis inhibition and G1-G2 arrest, reversed by the pancaspase inhibitor, zVAD-fmk, and associated with caspase-3 and -2 activation and CytC increase. Moreover, flavopiridol strongly down-regulated MYCN mRNA and protein expression. Exposure to hypoxia enhanced both the extent of apoptosis and flavopiridol effects on CytC, caspase 3, and MYCN.These results indicate that flavopiridol has growth-inhibitory and apoptotic activity against advanced-stage neuroblastomas in vitro and is worthy of further investigation for the treatment of this disease.
Preferential DNA Damage and Poor Repair Determine ras Gene Mutational Hotspot in Human Cancer
Authors: Z. Feng
Journal: JNCI Journal of the National Cancer Institute (2002)

Mutations in ras genes are commonly found in human cancers and in animal models. Although mutations at codons 12, 13, and 61 of H-, N- and K-ras genes can activate their oncogenic function, mutations at codon 12 of K-ras are the most common mutations found among the three ras genes in human cancers. To investigate whether codon 12 of human K-ras is especially susceptible to carcinogens and/or whether carcinogen-DNA adducts at this codon are repaired less efficiently, we examined tobacco smoke carcinogen-induced DNA damage in normal human bronchial epithelial and fibroblast cells.We used the UvrABC nuclease incision method in combination with ligation-mediated polymerase chain reaction to map the distribution of DNA adducts induced by benzo[a]pyrene diol epoxide (BPDE) and other bulky carcinogens within exons 1 and 2 in H-ras, N-ras, and K-ras. We also analyzed BPDE-DNA adduct repair efficiency in these three genes using the same method.Codons 12 and 14 of the K-ras gene were hotspots for carcinogen-DNA adduct formation, with little and no adduct formation at codons 13 and 61, respectively. The BPDE-DNA adducts formed at codon 14 were repaired almost twice as quickly as those formed at codon 12. There was some BPDE-DNA adduct formation at codons 12 of H-ras and N-ras, but this codon was not a hotspot. Furthermore, no substantial difference in repair rates between codon 12 and the other codons analyzed (codons 3 and 18) was observed in either the H-ras or N-ras genes.These findings link the human cancer mutational hotspot at codon 12 of K-ras to preferential DNA damage and poor repair.
Acquired Acrodermatitis Enteropathica
Authors: Gautam Naresh Mankaney, Kishore Vipperla
Journal: New England Journal of Medicine (2014)

A 54-year-old woman presented with an intractable rash that was not responsive to topical glucocorticoid and antifungal treatment. She had undergone bariatric surgery with Roux-en-Y gastric bypass about 8 years previously.