tbuckley/cabot-search huggingface dataset:
Calculating gambling odds and lung ages for smokers
Authors: J. E. Hansen, X-G. Sun, K. Wasserman
Journal: European Respiratory Journal (2009)

Interpreting spirometry as normal or abnormal using 95% confidence limits can obscure milder airflow decreases. Other analyses might better persuade cigarette smokers to quit. High-quality spirometric data of ambulatory never- and current-smokers of African-, European- and Latin-American ethnicity from the Third National Health and Nutrition Evaluation Survey (n&gt;9000) were analysed. We desired to calculate, for each decade of life, the odds that specific ratios of forced expiratory volume in 1 s to 6 s (%FEV 1 /FEV 6 ) and to forced vital capacity (%FEV 1 /FVC) values came from a current- or never-smoker. We also desired to develop new, simpler and better formulas to estimate changes in physiological lung age (Δlung age) for males and females. For each decade of life, odds increase strikingly that smoking decreases %FEV 1 /FEV 6 and %FEV 1 /FVC. At least for these three ethnicities, Δlung age can be easily calculated as the product of (predicted - actual) %FEV 1 /FEV 6 × 4 or (predicted - actual) %FEV 1 /FVC × 3. Through the sixth decade of life, smokers' Δlung age increase rapidly but little thereafter, presumably due to the inabilities of older smokers to participate in the survey or their deaths. Using odds and Δlung ages rather than traditional 95% confidence limits might better persuade smokers to quit.
Association Between the 21-Gene Recurrence Score Assay and Risk of Locoregional Recurrence in Node-Negative, Estrogen Receptor–Positive Breast Cancer: Results From NSABP B-14 and NSABP B-20
Authors: Eleftherios P. Mamounas, Gong Tang, Bernard Fisher, Soonmyung Paik, Steven Shak, Joseph P. Costantino, Drew Watson, Charles E. Geyer, D. Lawrence Wickerham, Norman Wolmark
Journal: Journal of Clinical Oncology (2010)

The 21-gene OncotypeDX recurrence score (RS) assay quantifies the risk of distant recurrence in tamoxifen-treated patients with node-negative, estrogen receptor (ER)-positive breast cancer. We investigated the association between RS and risk for locoregional recurrence (LRR) in patients with node-negative, ER-positive breast cancer from two National Surgical Adjuvant Breast and Bowel Project (NSABP) trials (NSABP B-14 and B-20).RS was available for 895 tamoxifen-treated patients (from both trials), 355 placebo-treated patients (from B-14), and 424 chemotherapy plus tamoxifen-treated patients (from B-20). The primary end point was time to first LRR. Distant metastases, second primary cancers, and deaths before LRR were censored.In tamoxifen-treated patients, LRR was significantly associated with RS risk groups (P < .001). The 10-year Kaplan-Meier estimate of LRR was 4.% (95% CI, 2.3% to 6.3%) for patients with a low RS (< 18), 7.2% (95% CI, 3.4% to 11.0%) for those with intermediate RS (18-30), and 15.8% (95% CI, 10.4% to 21.2%) for those with a high RS (> 30). There were also significant associations between RS and LRR in placebo-treated patients from B-14 (P = .022) and in chemotherapy plus tamoxifen-treated patients from B-20 (P = .028). In multivariate analysis, RS was an independent significant predictor of LRR along with age and type of initial treatment.Similar to the association between RS and risk for distant recurrence, a significant association exists between RS and risk for LRR. This information has biologic consequences and potential clinical implications relative to locoregional therapy decisions for patients with node-negative and ER-positive breast cancer.
Tissue- and development-specific expression of multiple alternatively spliced transcripts of rat neuronal nitric oxide synthase.
Authors: M A Lee, L Cai, N Hübner, Y A Lee, K Lindpaintner
Journal: Journal of Clinical Investigation (1997)

Nitric oxide (NO) functions as an intercellular messenger and mediates numerous biological functions. Among the three isoforms of NO synthase that produce NO, the ubiquitously expressed neuronal NO synthase (nNOS) is responsible for a large part of NO production, yet its regulation is poorly understood. Recent reports of two alternative spliceforms of nNOS in the mouse and in man have raised the possibility of spatial and temporal modulation of expression. This study demonstrates the existence of at least three transcripts of the rat nNOS gene designated nNOSa, nNOSb, and nNOSc, respectively, with distinct 5' untranslated first exons that arise from alternative splicing to a common second exon. Expression of the alternative transcripts occurs with a high degree of tissue and developmental specificity, as demonstrated by RNase protection assays on multiple tissues from both fetal and adult rats. Furthermore, terminal differentiation of rat pheochromocytoma-derived PC12 cells into neurons is associated with induction of nNOSa, suggesting, likewise, development- and tissue-specific transcriptional control of nNOS isoform expression. Physical mapping using a rat yeast artificial chromosome clone shows that the alternatively spliced first exons 1a, 1b, and 1c are separated by at least 15-60 kb from the downstream coding sequence, with exons 1b and 1c being positioned within 200 bp of each other. These findings provide evidence that the biological activity of nNOS is tightly and specifically regulated by a complex pattern of alternative splicing, indicating that the notion of constitutive expression of this isoform needs to be revised.
Magnetic resonance technology in training and sports
Authors: Thomas B Price
Journal: British Journal of Sports Medicine (2000)

When muscles are used to perform physical activity they must metabolise available fuel to generate energy for contraction. The harder a muscle must work, the more fuel is required. The relation between how hard muscles must work and their need for fuel is an area of intense interest in the study of human performance. In the past, intramuscular energy metabolism has been measured directly by muscle biopsies,1 which are invasive. During the last two decades, the sophistication of magnetic resonance (MR) technology has steadily improved. Using magnetic resonance spectroscopy (MRS), it is now possible to detect non-invasively changes in a number of important intramuscular fuel sources, such as muscle glycogen,2–5 during exercise and recovery. Magnetic resonance imaging (MRI) has been used for some time to examine anatomical effects of sport and training.6 Recently it has become possible to measure exercise induced physiological changes with MRI and use information from these measurements to determine muscle activity patterns.7–9 These more recent advances open up a new range of possibilities to use MR technology not only as a diagnostic tool, as in the past, but in …
Gastric Bypass Surgery in Severely Obese Women With Type 1 Diabetes: Anthropometric and Cardiometabolic Effects at 1 and 5 Years Postsurgery
Authors: Roeland J.W. Middelbeek, Tamarra James-Todd, Jerry D. Cavallerano, Deborah K. Schlossman, Mary Elizabeth Patti, Florence M. Brown
Journal: Diabetes Care (2015)

While the benefits of gastric bypass (GB) surgery in type 2 diabetes are well established, few studies have evaluated the long-term effects of GB in patients with type 1 diabetes (1,2), and these studies demonstrate conflicting effects on glycemic control. This is clinically important given the increasing prevalence of obesity in patients with type 1 diabetes (3). We studied 10 severely obese women with confirmed type 1 diabetes, as previously described (4), and evaluated outcomes prior to GB and at 1 and 5 years following surgery. Mean age at GB was 39.6 ± 8.4 years, mean duration of type 1 diabetes 24.6 ± 10.1 years, and mean age at diagnosis 16.0 ± 8.3 years. Six subjects used continuous subcutaneous insulin infusion.

BMI decreased by 33% from baseline at 1 year postoperatively (from 43.5 ± 7.5 to 29.3 ± 5.4 kg/m2, P < 0.0001) but …
Phase III Study Comparing Amrubicin Plus Cisplatin With Irinotecan Plus Cisplatin in the Treatment of Extensive-Disease Small-Cell Lung Cancer: JCOG 0509
Authors: Miyako Satouchi, Yoshikazu Kotani, Taro Shibata, Masahiko Ando, Kazuhiko Nakagawa, Nobuyuki Yamamoto, Yukito Ichinose, Yuichiro Ohe, Makoto Nishio, Toyoaki Hida, Koji Takeda, Tatsuo Kimura, Koichi Minato, Akira Yokoyama, Shinji Atagi, Haruhiko Fukuda, Tomohide Tamura, Nagahiro Saijo
Journal: Journal of Clinical Oncology (2014)

This randomized phase III trial was conducted to confirm noninferiority of amrubicin plus cisplatin (AP) compared with irinotecan plus cisplatin (IP) in terms of overall survival (OS) in chemotherapy-naive patients with extensive-disease (ED) small-cell lung cancer (SCLC).Chemotherapy-naive patients with ED-SCLC were randomly assigned to receive IP, composed of irinotecan 60 mg/m(2) on days 1, 8, and 15 and cisplatin 60 mg/m(2) on day 1 every 4 weeks, or AP, composed of amrubicin 40 mg/m(2) on days 1, 2, and 3 and cisplatin 60 mg/m(2) on day 1 every 3 weeks.A total of 284 patients were randomly assigned to IP (n = 142) and AP (n = 142) arms. The point estimate of OS hazard ratio (HR) for AP to IP in the second interim analysis exceeded the noninferior margin (HR, 1.31), resulting in early publication because of futility. In updated analysis, median survival time was 17.7 (IP) versus 15.0 months (AP; HR, 1.43; 95% CI, 1.10 to 1.85), median progression-free survival was 5.6 (IP) versus 5.1 months (AP; HR, 1.42; 95% CI, 1.16 to 1.73), and response rate was 72.3% (IP) versus 77.9% (AP; P = .33). Adverse events observed in IP and AP arms were grade 4 neutropenia (22.5% v 79.3%), grade 3 to 4 febrile neutropenia (10.6% v 32.1%), and grade 3 to 4 diarrhea (7.7% v 1.4%).AP proved inferior to IP in this trial, perhaps because the efficacy of amrubicin as a salvage therapy was differentially beneficial to IP. IP remains the standard treatment for extensive-stage SCLC in Japan.
Peripheral T-cell lymphoma unspecified (PTCL-U): a new prognostic model from a retrospective multicentric clinical study
Authors: Andrea Gallamini, Caterina Stelitano, Roberta Calvi, Monica Bellei, Daniele Mattei, Umberto Vitolo, Fortunato Morabito, Maurizio Martelli, Ercole Brusamolino, Emilio Iannitto, Francesco Zaja, Sergio Cortelazzo, Luigi Rigacci, Liliana Devizzi, Giuseppe Todeschini, Gino Santini, Maura Brugiatelli, Massimo Federico
Journal: Blood (2003)
World cup soccer players tend to be born with sun and moon in adjacent zodiacal signs
Authors: J Verhulst
Journal: British Journal of Sports Medicine (2000)

The ecliptic elongation of the moon with respect to the sun does not show uniform distribution on the birth dates of the 704 soccer players selected for the 1998 World Cup. However, a uniform distribution is expected on astronomical grounds. The World Cup players show a very pronounced tendency (p = 0.00001) to be born on days when the sun and moon are in adjacent zodiacal signs.
Canonical Wnt Signaling Is Required for Pancreatic Carcinogenesis
Authors: Yaqing Zhang, John P. Morris, Wei Yan, Heather K. Schofield, Austin Gurney, Diane M. Simeone, Sarah E. Millar, Timothy Hoey, Matthias Hebrok, Marina Pasca di Magliano
Journal: Cancer Research (2013)

Abstract Wnt ligand expression and activation of the Wnt/β-catenin pathway have been associated with pancreatic ductal adenocarcinoma, but whether Wnt activity is required for the development of pancreatic cancer has remained unclear. Here, we report the results of three different approaches to inhibit the Wnt/β-catenin pathway in a established transgenic mouse model of pancreatic cancer. First, we found that β-catenin null cells were incapable of undergoing acinar to ductal metaplasia, a process associated with development of premalignant pancreatic intraepithelial neoplasia lesions. Second, we addressed the specific role of ligand-mediated Wnt signaling through inducible expression of Dkk1, an endogenous secreted inhibitor of the canonical Wnt pathway. Finally, we targeted the Wnt pathway with OMP-18R5, a therapeutic antibody that interacts with multiple Frizzled receptors. Together, these approaches showed that ligand-mediated activation of the Wnt/β-catenin pathway is required to initiate pancreatic cancer. Moreover, they establish that Wnt signaling is also critical for progression of pancreatic cancer, a finding with potential therapeutic implications. Cancer Res; 73(15); 4909–22. ©2013 AACR.
A prospective study of diet and adult-onset asthma.
Authors: R J Troisi, W C Willett, S T Weiss, D Trichopoulos, B Rosner, F E Speizer
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

A role for diet in the pathophysiology of asthma may be mediated by altered immune or antioxidant activity with consequent effects on airway inflammation. We evaluated associations between several dietary factors assessed by a semiquantitative food frequency questionnaire, and incidence of asthma over a 10-yr period in 77,866 women 34 to 68 yr of age. Women in the highest quintile of vitamin E intake from diet, but not from supplements, had a risk of 0.53 (95% confidence interval [CI] = 0.33 to 0.86) compared with women in the lowest quintile. This relationship, however, was attenuated when the contribution from nuts, a major source of vitamin E in these data and a possible allergen, was removed (relative risk = 0.74 [0.50 to 1.10], p for trend = 0.007). Positive associations were found for vitamins C and E from supplements, but appeared to be explained by women at high risk of asthma initiating use of vitamin supplements prior to diagnosis. A nonsignificant inverse association with carotene intake was noted, but no clear relations with asthma were demonstrated for intake of linoleic acid or omega-3 fatty acids. These data suggest that antioxidant supplementation and intake of various fats during adulthood are not important determinants of asthma, although vitamin E from diet may have a modest protective effect.
Ontogeny of B-lymphocyte function. II. Ability of endotoxin to increase the heterogeneity of affinity of the immune response of B lymphocytes from fetal mice.
Authors: E A Goidl, J Klass, G W Siskind
Journal: The Journal of Experimental Medicine (1976)

The ontogeny of the functional capacity of B lymphocytes to generate a heterogeneous response to a haptenic determinant was studied by cell transfer techniques in LAF1 mice. Fetal liver, as a source of B lymphocytes, was transferred into adult, syngeneic, irradiated animals. All recipients received excess adult thymus cells so that T-cell activity did not limit the response and were immunized with DNP-BGG. The heterogeneity of avidity of their anti-DNP PFC response was assayed by hapten inhibition of plaque formation. Animals reconstituted with B lymphocytes from fetal donors produced a response that is highly restricted with respect to heterogeneity of affinity. Transfer studies using multiple fetal donors or mixtures of adult and neonatal cells for reconstitution suggest that the restriction in heterogeneity is not the consequence of suppressor T-lymphocyte activity. With animals reconstituted with B cells from day 16 or older fetal donors, injection of LPS together with antigen converted the response to a heterogeneous "adult-type" response. With animals reconstituted with B lymphocytes from day 14 fetal liver DxSO4, but not LPS, could convert the response to a highly heterogeneous one. Animals reconstituted with day 14 or 16 fetal liver as source of B lymphocytes were capable of producing a heterogeneous secondary response despite the fact that their primary response was of restricted heterogeneity. This implies the selection of high affinity B-memory cells, in the absence of high affinity PFC during the primary response with fetal B lymphocytes. Animals reconstituted with day 14 or 16 fetal liver produce only direct PFC, while animals reconstituted with day 18 fetal liver produce both direct and indirect PFC. Three differentiation events have therefore been defined in the functional development of B lymphocytes: (a) between day 14 and day 16 of fetal life they acquire responsiveness to LPS; (B) BETWEEN DAY 16 AND 18 OF FETAL DEVELOPMENT THEY ACQUire the capacity to produce indirect PFC; (C) between day 7 and 10 after birth they acquire the capacity to give a heterogeneous response after normal immunization. In addition, it was shown that LAF1 mice already have all of the information required to produce an "adult-type" heterogeneous anti-DNP response at day 14 of fetal life.
Cell Biological and Biochemical Characterization of Drebrin Complexes in Mesangial Cells and Podocytes of Renal Glomeruli
Authors: Wiebke K. Peitsch, Ilse Hofmann, Nicole Endlich, Silke Prätzel, Cäcilia Kuhn, Herbert Spring, Hermann-Josef Gröne, Wilhelm Kriz, Werner W. Franke
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Drebrins are actin-binding proteins (ABP) initially identified in and thought to be specific for neuronal cells, where they appear to contribute to the formation of cell processes. Recent studies have also detected the isoform drebrin E2 in a wide range of non-neuronal cell types, notably in and near actin-rich lamellipodia and filopodia. The present study demonstrates drebrin enrichment in renal glomeruli. Immunohistochemistry and double-label confocal laser scanning microscopy have shown intense drebrin reactions in the mesangial cells of diverse mammalian species. In adult human and bovine kidneys, drebrin is, in addition, markedly enriched in the foot processes of podocytes, as also demonstrable by immunoelectron microscopy. By contrast, the podocytes of rodent glomeruli appear to contain significant drebrin concentrations only during early developmental stages. In differentiated murine podocytes cultured in vitro, however, drebrin is concentrated in the cell processes, where it partially codistributes with actin and other ABP. In biochemical analyses using protein extracts from renal cortices, large (approximately 20S) complexes ("drebrosomes") were found containing drebrin and actin. These findings confirm and extend our hypothesis that drebrin is involved in the regulation of actin dynamics also outside the nervous system. Clearly, drebrin has to be added to the ensemble of ABP regulating the actomyosin system and the dynamics of mesangial cells and foot processes in podocytes. E-mail: [email protected]
Coronary artery-left ventricular fistula and multiple ventricular septal defects due to blunt chest trauma.
Authors: A Renzulli, C Wren, C J Hilton
Journal: Thorax (1989)

A 27 year old man developed multiple ventricular septal defects and a coronary artery ventricular fistula after a blunt injury. These were treated successfully by surgery, which was carried out four months after the injury to allow some healing of the defect to occur.
Treatment and outcome in an unselected elderly population with acute myocardial infarction: data from the AMI florence registry
Authors: Nazario Carrabba, Alessandro Barchielli, Giovanni Maria Santoro, Giorgio Corti, Francesco Ferrante, Maurizio Filice, Marcella Maci, Niccolò Marchionni, Eva Buiatti
Journal: Journal of the American College of Cardiology (2002)
Copy Number Alterations among Mammalian Enzymes Cluster in the Metabolic Network
Authors: M. Bekaert, G. C. Conant
Journal: Molecular Biology and Evolution (2010)

Using two high-quality human metabolic networks, we employed comparative genomics techniques to infer metabolic network structures for seven other mammals. We then studied copy number alterations (CNAs) in these networks. Using a graph-theoretic approach, we show that the pattern of CNAs is distinctly different from the random distributions expected under genetic drift. Instead, we find that changes in copy number are most common among transporter genes and that the CNAs differ depending on the mammalian lineage in question. Thus, we find an excess of transporter genes in cattle involved in the milk production, secretion, and regulation. These results suggest a potential role for dosage selection in the evolution of mammalian metabolic networks.
Identification of biliprotein as a liver growth factor
Authors: Juan J. Díaz-Gil, Gonzalo Sánchez, Carolina Trilla, Pedro Escartín
Journal: Hepatology (1988)

We determined the concentration of biliprotein in plasma of rats at different times after partial hepatectomy. From the same plasma samples, we purified a liver growth factor previously characterized by our group. When we plotted the 14 points studied, a linear relationship was obtained (r = 0.999; p &lt; 0.001). This result, in addition to our group’s recent identification of this liver growth factor as an albumin-bilirubin complex, strongly suggests that biliprotein is a liver growth factor.
Activation of Phosphatidylinositol 3-Kinase and Extracellular Signal-Regulated Kinase Is Required for Glial Cell Line-Derived Neurotrophic Factor-Induced Migration and Invasion of Pancreatic Carcinoma Cells
Authors: Christine Veit, Felicitas Genze, Andre Menke, Silke Hoeffert, Thomas M. Gress, Peter Gierschik, Klaudia Giehl
Journal: Cancer Research (2004)

Abstract Pancreatic carcinoma cells exhibit a pronounced tendency to invade along and into intra- and extrapancreatic nerves, even at early stages of the disease. The neurotrophic factor glial cell line-derived neurotrophic factor (GDNF) has been shown to promote pancreatic cancer cell invasion. Here, we demonstrate that pancreatic carcinoma cell lines, such as PANC-1, expressed the RET and GDNF family receptor α receptor components for GDNF and that primary pancreatic tumor samples, derived from carcinomas with regional lymph node metastasis, exhibited marked expression of the mRNA encoding the RET51 isoform. Moreover, GDNF was an efficacious and potent chemoattractant for pancreatic carcinoma cells as examined in in vitro and in vivo model systems. Treatment of PANC-1 cells with GDNF resulted in activation of the monomeric GTPases N-Ras, Rac1, and RhoA, in activation of the mitogen-activated protein kinases extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) and in activation of the phosphatidylinositol 3-kinase/Akt pathway. Both inhibition of the Ras-Raf-MEK (mitogen-activated protein/ERK kinase)-ERK cascade by either stable expression of dominant-negative H-Ras(N17) or addition of the MEK1 inhibitor PD98059 as well as inhibition of the phosphatidylinositol 3-kinase pathway by LY294002 prevented GDNF-induced migration and invasion of PANC-1 cells. These results demonstrate that pancreatic tumor cell migration and possibly perineural invasion in response to GDNF is critically controlled by activation of the Ras-Raf-MEK-ERK and the phosphatidylinositol 3-kinase pathway.
Analysis of Time-Series Gene Expression Data: Methods, Challenges, and Opportunities
Authors: I.P. Androulakis, E. Yang, R.R. Almon
Journal: Annual Review of Biomedical Engineering (2007)

Monitoring the change in expression patterns over time provides the distinct possibility of unraveling the mechanistic drivers characterizing cellular responses. Gene arrays measuring the level of mRNA expression of thousands of genes simultaneously provide a method of high-throughput data collection necessary for obtaining the scope of data required for understanding the complexities of living organisms. Unraveling the coherent complex structures of transcriptional dynamics is the goal of a large family of computational methods aiming at upgrading the information content of time-course gene expression data. In this review, we summarize the qualitative characteristics of these approaches, discuss the main challenges that this type of complex data present, and, finally, explore the opportunities in the context of developing mechanistic models of cellular response.
Plastic, fantastic! Phenotypic variance in the transcriptional landscape of the grape berry
Authors: Alisdair R Fernie, Takayuki Tohge
Journal: Genome biology (2013)

Evaluation of the common grapevine Vitis vinifera across multiple harvests and field locations provides important insights into crop transcriptional plasticity under diverse agricultural regimes. Please see related Research: http://genomebiology.com/2013/14/6/R54