tbuckley/cabot-search huggingface dataset:
Intratracheal Administration of Budesonide/Surfactant to Prevent Bronchopulmonary Dysplasia
Authors: Tsu F. Yeh, Chung M. Chen, Shou Y. Wu, Zahid Husan, Tsai C. Li, Wu S. Hsieh, Chang H. Tsai, Hung C. Lin
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Bronchopulmonary dysplasia (BPD) is an important complication of mechanical ventilation in preterm infants, and no definite therapy can eliminate this complication. Pulmonary inflammation plays a crucial role in its pathogenesis, and glucocorticoid is one potential therapy to prevent BPD.To compare the effect of intratracheal administration of surfactant/budesonide with that of surfactant alone on the incidence of death or BPD.A clinical trial was conducted in three tertiary neonatal centers in the United States and Taiwan, in which 265 very-low-birth-weight infants with severe respiratory distress syndrome who required mechanical ventilation and inspired oxygen (fraction of inspired oxygen, ≥50%) within 4 hours of birth were randomly assigned to one of two groups (131 intervention and 134 control). The intervention infants received surfactant (100 mg/kg) and budesonide (0.25 mg/kg), and the control infants received surfactant only (100 mg/kg), until each infant required inspired O2 at less than 30% or was extubated.The intervention group had a significantly lower incidence of BPD or death (55 of 131 [42.0%] vs. 89 of 134 [66%]; risk ratio, 0.58; 95% confidence interval, 0.44-0.77; P < 0.001; number needed to treat, 4.1; 95% confidence interval, 2.8-7.8). The intervention group required significantly fewer doses of surfactant than did the control group. The intervention group had significantly lower interleukin levels (IL-1, IL-6, IL-8) in tracheal aspirates at 12 hours and lower IL-8 at 3-5 and 7-8 days.In very-low-birth-weight infants with severe respiratory distress syndrome, intratracheal administration of surfactant/budesonide compared with surfactant alone significantly decreased the incidence of BPD or death without immediate adverse effect. Clinical trial registered with www.clinicaltrials.gov (NCT-00883532).
P0760 : PNPLA3 rs738409 I748M is associated with steatohepatitis in non obese subjects with hepatitis C
Authors: S. Petta, E. Vanni, E. Bugianesi, C. Rosso, D. Cabibi, C. Cammà, V. Di Marco, M. Eslam, S. Grimaudo, F.S. Macaluso, D. McLeod, R.M. Pipitone, M.L. Abate, A. Smedile, J. George, A. Craxì
Journal: Journal of Hepatology (2015)
Clinical Significance of CXC Chemokine Receptor-4 and c-Met in Childhood Rhabdomyosarcoma
Authors: Francesca Diomedi-Camassei, Heather P. McDowell, Maria A. De Ioris, Stefania Uccini, Pierluigi Altavista, Giuseppe Raschellà, Roberta Vitali, Olga Mannarino, Luigi De Sio, Denis A. Cozzi, Alberto Donfrancesco, Alessandro Inserra, Francesco Callea, Carlo Dominici
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The CXC chemokine receptor-4 (CXCR4)/stromal-derived factor-1 and c-Met/hepatocyte growth factor axes promote the metastatic potential of rhabdomyosarcoma cell lines in experimental models, but no data are available on their role in rhabdomyosarcoma tumors. The expressions of CXCR4 and c-Met were evaluated in primary tumors and isolated tumor cells in marrow, and were correlated with clinicopathologic variables and survival. Experimental Design: Forty patients with recently diagnosed rhabdomyosarcoma were retrospectively enrolled. CXCR4 and c-Met expression was investigated in primary tumors by immunohistochemistry, in isolated marrow-infiltrating tumor cells using double-label immunocytology. Results were expressed as the mean percentage of immunostained tumor cells. Results: CXCR4 and c-Met were expressed in ≥5% of tumor cells from 40 of 40 tumors, with 14 of 40 cases showing ≥50% of immunostained tumor cells (high expression). High CXCR4 expression correlated with alveolar histology (P = 0.006), unfavorable primary site (P = 0.009), advanced group (P &amp;lt; 0.001), marrow involvement (P = 0.007), and shorter overall survival and event-free survival (P &amp;lt; 0.001); high c-Met expression correlated with alveolar histology (P = 0.005), advanced group (P = 0.04), and marrow involvement (P = 0.02). In patients with a positive diagnosis for isolated tumor cells in marrow (n = 16), a significant enrichment in the percentage of CXCR4-positive (P = 0.001) and c-Met–positive (P = 0.003) tumor cells was shown in marrow aspirates compared with the corresponding primary tumors. Conclusions: CXCR4 and c-Met are widely expressed in both rhabdomyosarcoma subtypes and, at higher levels, in isolated marrow-infiltrating tumor cells. High levels of expression are associated with unfavorable clinical features, tumor marrow involvement and, only for CXCR4, poor outcome. In rhabdomyosarcoma, CXCR4 and c-Met represent novel exploitable targets for disease-directed therapy.
Selection on cis-Regulatory Variation at B4galnt2 and Its Influence on von Willebrand Factor in House Mice
Authors: J. M. Johnsen, M. Teschke, P. Pavlidis, B. M. McGee, D. Tautz, D. Ginsburg, J. F. Baines
Journal: Molecular Biology and Evolution (2008)

The RIIIS/J inbred mouse strain is a model for type 1 von Willebrand disease (VWD), a common human bleeding disorder. Low von Willebrand factor (VWF) levels in RIIIS/J are due to a regulatory mutation, Mvwf1, which directs a tissue-specific switch in expression of a glycosyltransferase, B4GALNT2, from intestine to blood vessel. We recently found that Mvwf1 lies on a founder allele common among laboratory mouse strains. To investigate the evolutionary forces operating at B4galnt2, we conducted a survey of DNA sequence polymorphism and microsatellite variation spanning the B4galnt2 gene region in natural Mus musculus domesticus populations. Two divergent haplotypes segregate in these natural populations, one of which corresponds to the RIIIS/J sequence. Different local populations display dramatic differences in the frequency of these haplotypes, and reduced microsatellite variability near B4galnt2 within the RIIIS/J haplotype is consistent with the recent action of natural selection. The level and pattern of DNA sequence polymorphism in the 5' flanking region of the gene significantly deviates from the neutral expectation and suggests that variation in B4galnt2 expression may be under balancing selection and/or arose from a recently introgressed allele that subsequently increased in frequency due to natural selection. However, coalescent simulations indicate that the heterogeneity in divergence between haplotypes is greater than expected under an introgression model. Analysis of a population where the RIIIS/J haplotype is in high frequency reveals an association between this haplotype, the B4galnt2 tissue-specific switch, and a significant decrease in plasma VWF levels. Given these observations, we propose that low VWF levels may represent a fitness cost that is offset by a yet unknown benefit of the B4galnt2 tissue-specific switch. Similar mechanisms may account for the variability in VWF levels and high prevalence of VWD in other mammals, including humans.
Effects of Chronic and Acute Ozone Exposure on Lipid Peroxidation and Antioxidant Capacity in Healthy Young Adults
Authors: Connie Chen, Mehrdad Arjomandi, John Balmes, Ira Tager, Nina Holland
Journal: Environmental Health Perspectives (2007)

BackgroundThere is growing evidence for the role of oxidative damage in chronic diseases. Although ozone (O3) is an oxidant pollutant to which many people are exposed, few studies have examined whether O3 induces oxidative stress in humans.ObjectivesThis study was designed to assess the effect of short-and long-term O3 exposures on biomarkers of oxidative stress in healthy individuals.MethodsBiomarkers of lipid peroxidation, 8-isoprostane (8-iso-PGF), and antioxidant capacity ferric reducing ability of plasma (FRAP) were analyzed in two groups of healthy college students with broad ranges of ambient O3 exposure during their lifetimes and previous summer recess either in Los Angeles (LA, n = 59) or the San Francisco Bay Area (SF, n = 61).ResultsEstimated 2-week, 1-month, and lifetime O3 exposures were significantly correlated with elevated 8-iso-PGF. Elevated summertime exposures resulted in the LA group having higher levels of 8-iso-PGF than the SF group (p = 0.02). Within each location, males and females had similar 8-iso-PGF. No regional difference in FRAP was observed, with significantly higher FRAP in males in both groups (SF: p = 0.002; LA: p = 0.004). An exposure chamber substudy (n = 15) also showed a significant increase in 8-iso-PGF as well as an inhibition of FRAP immediately after a 4-hr exposure to 200 ppb O3, with near normalization by 18 hr in both biomarkers.ConclusionsLong-term exposure to O3 is associated with elevated 8-iso-PGF, which suggests that 8-iso-PGF is a good biomarker of oxidative damage related to air pollution.
ASSESSING REMEDIES FOR MISSING WEEKLY INDIVIDUAL EXPOSURE IN SPORT INJURY STUDIES
Authors: J Kang, Y Yuan, C Emery
Journal: British Journal of Sports Medicine (2014)

Background In sport injury epidemiology research, the injury incidence rate (IR) is defined as the number of injuries over a given length of participation time (exposure, e.g. game hours). However, it is common that individual weekly exposure is missing due to requirements of personnel at every game to record exposure information. Ignoring this issue will lead to an inflated injury rate because the total exposure serves as the denominator of IR, where the number of injury cases were captured accurately. Objective To compare 6 methods to handle missing weekly exposure of individual players. Design Data collected from a large community cohort study in youth ice hockey. Setting Youth ice hockey. Participants Pee Wee (age 11–12) ice hockey players. Interventions The 6 methods to handle missing weekly exposures include available case analysis, last-observation-carried-forward, mean imputation, multiple imputation, bootstrapping, and best/worst case analysis. Main outcome measures Injury rate ratios (IRR) between Alberta and Quebec, as in the original study, three statistical models were applied to the imputed datasets: Poisson, zero-inflated Poisson, and negative binomial regression models. Results The final sample for imputation included 2098 players for whom 12.5% of weekly game hours were missing. Estimated IRs and IRRs with confidence intervals from different imputation methods were similar when the proportion of missing was small. Simulations showed that mean and multiple imputations provide the least biased estimates of IRR when the proportion of missing was large. Conclusion Complicated methods like multiple imputation or bootstrap are not superior over the mean imputation, a much simpler method, in handling missing weekly exposure of injury data where weekly exposures were missing at random.
Generalized eruptive keratoacanthoma (Grzybowski variant)
Authors: J.E. Consigli, M.E. GonzÁlez, R. Morsino, A. Guidi, J.M. Chappuis, M. Papa, S. Maldonado
Journal: British Journal of Dermatology (2000)

We describe a patient with generalized eruptive keratoacanthoma (KA) of Grzybowski showing the characteristic features of this extremely rare condition. Since the first description by Grzybowski in 1950, only 28 additional cases (including the present one) have been reported. This variety of KA most commonly affects patients during the fifth to seventh decade of life and appears as a generalized eruption of hundreds to thousands of follicular papules. The small pruriginous papules often have a keratotic centre and show microscopic features of KA. Marked facial involvement is characteristic and can lead to masked facies with ectropion, as in our patient. The course of the disease is chronic and the response to therapy is poor.
Association of Inflammation-Related and microRNA Gene Expression with Cancer-Specific Mortality of Colon Adenocarcinoma
Authors: Aaron J. Schetter, Giang Huong Nguyen, Elise D. Bowman, Ewy A. Mathé, Siu Tsan Yuen, Jason E. Hawkes, Carlo M. Croce, Suet Yi Leung, Curtis C. Harris
Journal: Clinical Cancer Research (2009)

Inflammatory genes and microRNAs have roles in colon carcinogenesis; therefore, they may provide useful biomarkers for colon cancer. This study examines the potential clinical utility of an inflammatory gene expression signature as a prognostic biomarker for colon cancer in addition to previously examined miR-21 expression.Quantitative reverse transcriptase-PCR. was used to measure the expression of 23 inflammatory genes in colon adenocarcinomas and adjacent noncancerous tissues from 196 patients. These data were used to develop models for cancer-specific mortality on a training cohort (n = 57), and this model was tested in both a test (n = 56) and a validation (n = 83) cohort. Expression data for miR-21 were available for these patients and were compared and combined with inflammatory gene expression.PRG1, IL-10, CD68, IL-23a, and IL-12a expression in noncancerous tissue, and PRG1, ANXA1, IL-23a, IL-17a, FOXP3, and HLA-DRA expression in tumor tissues were associated with poor prognosis based on Cox regression (/Z-score/ >1.5) and were used to generate the inflammatory risk score (IRS). IRS was associated with cancer-specific mortality in the training, test (P = 0.01), and validation (P = 0.02) cohorts. This association was strong for stage II cases (P = 0.002). Expression of miR-21 was associated with IL-6, IL-8, IL-10, IL-12a, and NOS2a, providing evidence that the function of this microRNA and these inflammatory genes are linked. Both IRS and miR-21 expression were independently associated with cancer-specific mortality, including stage II patients alone.IRS and miR-21 expression are independent predictors of colon cancer prognosis and may provide a clinically useful tool to identify high-risk patients.
<i>Trp53</i>Inactivation in the Tumor Microenvironment Promotes Tumor Progression by Expanding the Immunosuppressive Lymphoid-like Stromal Network
Authors: Gang Guo, Luis Marrero, Paulo Rodriguez, Luis Del Valle, Augusto Ochoa, Yan Cui
Journal: Cancer Research (2013)

Abstract Inactivation of the tumor suppressor p53 through somatic mutations, observed in 50% of human cancers, is one of the leading causes of tumorigenesis. Clinical and experimental evidence also reveals that p53 mutations sometimes occur in tumor-associated fibroblasts, which correlate with an increased rate of metastases and poor prognosis, suggesting that p53 dysfunction in the tumor microenvironment (TME) favors tumor establishment and progression. To understand the impact of p53 inactivation in the TME in tumor progression, we compared the growth of subcutaneously inoculated B16F1 melanoma in p53null and wild-type (WT) mice. Interestingly, tumor growth in p53null mice was greatly accelerated, correlating with marked increases in CD11b+Gr-1+ myeloid-derived suppressor cells (MDSC), FoxP3+ regulatory T cells, and a loss of effector function, compared with those in WT mice. This augmented immunotolerant TME in p53null mice was associated with a marked expansion of a specialized stromal network in the tumor and spleen. These stromal cells expressed markers of fibroblastic reticular cells of lymphoid organs and were readily expanded in culture from p53null, but not WT, mice. They produced high levels of inflammatory cytokines/chemokines and immunosuppressive molecules, thereby enhancing MDSC differentiation. Furthermore, they significantly accelerated tumor progression in WT mice when co-injected with B16F1. Together, our results show that tumor-stroma interaction in hosts with dysfunctional p53 exacerbates immunosuppression by expanding the lymphoid-like stromal network that enhances MDSC differentiation and tumor progression. Cancer Res; 73(6); 1668–75. ©2012 AACR.
The assessment and management of adults with status asthmaticus.
Authors: T C Corbridge, J B Hall
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Despite advancing knowledge of the pathophysiology and treatment of asthma, asthma morbidity and mortality are on the rise. To help avert this trend, clinicians and patients must focus their attention on the early identification and treatment of asthma exacerbations. As in the words of Dr. Thomas Petty: " ... the best treatment of status asthmaticus is to treat it three days before it occurs." (7) Still, there will be asthmatics with life-threatening attacks that require careful assessment and aggressive management. Inhaled beta-agonists, systemic corticosteroids, and oxygen remain the drugs of choice in SA. Anticholinergics play a lesser role in the treatment of acute asthma, and debate continues regarding the efficacy of theophylline in this setting. Available data do not support the routine use of magnesium sulfate or antibiotics in patients with SA. Patients failing drug therapy should be considered early for intubation and mechanical ventilation. A strategy of mechanical ventilation that prolongs TE by limiting VE and decreasing inspiratory time, and that tolerates hypercapnia, avoids excessive lung hyperinflation and barotrauma and should improve the outcome of these most critically ill asthmatics. Intubated and mechanically ventilated patients should be aggressively sedated. Paralytic agents should be used only if adequate control of the cardiopulmonary status cannot be achieved by sedation alone. Minimizing the use of paralytic agents may decrease risk of myopathy and other adverse consequences of muscle paralysis. Finally, after successful treatment of a life-threatening episode of asthma, the treatment team should address prevention of future episodes of SA prior to discharge.
Précis of<i>The creative mind: Myths and mechanisms</i>
Authors: Margaret A. Boden
Journal: Behavioral and Brain Sciences (1994)

Abstract What is creativity? One new idea may be creative, whereas another is merely new: What's the difference? And how is creativity possible? These questions about human creativity can be answered, at least in outline, using computational concepts. There are two broad types of creativity, improbabilist and impossibilist. Improbabilist creativity involves (positively valued) novel combinations of familiar ideas. A deeper type involves METCS: the mapping, exploration, and transformation of conceptual spaces. It is impossibilist, in that ideas may be generated which – with respect to the particular conceptual space concerned – could not have been generated before. (They are made possible by some transformation of the space.) The more clearly conceptual spaces can be defined, the better we can identify creative ideas. Defining conceptual spaces is done by musicologists, literary critics, and historians of art and science. Humanist studies, rich in intuitive subtleties, can be complemented by the comparative rigour of a computational approach. Computational modelling can help to define a space, and to show how it may be mapped, explored, and transformed. Impossibilist creativity can be thought of in “classical” Al terms, whereas connectionism illuminates improbabilist creativity. Most Al models of creativity can only explore spaces, not transform them, because they have no self-reflexive maps enabling them to change their own rules. A few, however, can do so. A scientific understanding of creativity does not destroy our wonder at it, nor does it make creative ideas predictable. Demystification does not imply dehumanization.
Effect of BRCA1 and XPG mutations on treatment response to trabectedin and pegylated liposomal doxorubicin in patients with advanced ovarian cancer: exploratory analysis of the phase 3 OVA-301 study
Authors: B.J. Monk, P. Ghatage, T. Parekh, E. Henitz, R. Knoblauch, A.S. Matos-Pita, A. Nieto, Y.C. Park, P.S. Cheng, W. Li, R. Favis, D. Ricci, A. Poveda
Journal: Annals of Oncology (2015)
Regulation of Pancreatic Tumor Cell Proliferation and Chemoresistance by the Histone Methyltransferase Enhancer of Zeste Homologue 2
Authors: Andrei V. Ougolkov, Vladimir N. Bilim, Daniel D. Billadeau
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Enhancer of zeste homologue 2 (EZH2), a histone methyltransferase, plays a key role in transcriptional repression through chromatin remodeling. Our objectives were to determine the expression pattern of EZH2 and to assess the anticancer effect of EZH2 depletion in pancreatic cancer cells. Experimental Design: Immunohistochemistry and cytosolic/nuclear fractionation were done to determine the expression pattern of EZH2 in normal pancreas and human pancreatic tumors. We used RNA interference, Western blotting, reverse transcription-PCR, and chromatin immunoprecipitation to study the effect of EZH2 depletion on pancreatic cancer cell proliferation and survival. Results: We detected nuclear overexpression of EZH2 in pancreatic cancer cell lines and in 71 of 104 (68%) cases of human pancreatic adenocarcinomas. EZH2 nuclear accumulation was more frequent in poorly differentiated pancreatic adenocarcinomas (31 of 34 cases; P &amp;lt; 0.001). We found that genetic depletion of EZH2 results in reexpression of p27Kip1 and decreased pancreatic cancer cell proliferation. Moreover, we showed that EZH2 depletion sensitized pancreatic cancer cells to doxorubicin and gemcitabine, which leads to a significant induction of apoptosis, suggesting that the combination of EZH2 inhibitors and standard chemotherapy could be a superior potential treatment for pancreatic cancer. Conclusions: Our results show nuclear accumulation of EZH2 as a hallmark of poorly differentiated pancreatic adenocarcinoma; identify the tumor suppressor p27Kip1 as a new target gene of EZH2; show that EZH2 nuclear overexpression contributes to pancreatic cancer cell proliferation; and suggest EZH2 as a potential therapeutic target for the treatment of pancreatic cancer.
Decreasing fibrogenesis: an immunohistochemical study of paired liver biopsies following lamivudine therapy for chronic hepatitis B
Authors: Young-Oh Kweon, Zachary D Goodman, Jules L Dienstag, Eugene R Schiff, Nathaniel A Brown, Elmar Burkhardt, Robert Schoonhoven, David A Brenner, Michael W Fried
Journal: Journal of Hepatology (2001)
Murine Monocyte Chemoattractant Protein (MCP)-5: A Novel CC Chemokine That Is a Structural and Functional Homologue of Human MCP-1
Authors: Mindy N. Sarafi, Eduardo A. Garcia-Zepeda, James A. MacLean, Israel F. Charo, Andrew D. Luster
Journal: The Journal of Experimental Medicine (1997)

The chemokines are a large family of cytokines that control the recruitment of leukocytes in immune and inflammatory responses. We describe the isolation of a novel murine CC chemokine that, based on its biological and structural features, we have named monocyte chemoattractant protein (MCP)-5. MCP-5 mapped to the CC chemokine cluster on mouse chromosome 11 and was most closely related to human MCP-1 in structure (66% amino acid identity). Purified recombinant MCP-5 protein was a potent chemoattractant for peripheral blood monocytes, was only weakly active on eosinophils at high doses, and was inactive on neutrophils. MCP-5 induced a calcium flux in peripheral blood mononuclear cells, but not in purified murine eosinophils or neutrophils. Consistent with these results, MCP-5 induced a calcium flux in human embryonic kidney (HEK)-293 cells transfected with human and murine CCR2, a CC chemokine receptor expressed on monocytes. MCP-5 did not induce a calcium flux in HEK-293 cells transfected with CCR1, CCR3, or CCR5. Constitutive expression of MCP-5 mRNA was detected predominantly in lymph nodes, and its expression was markedly induced in macrophages activated in vitro and in vivo. Moreover, MCP-5 expression was upregulated in the lungs of mice following aerosolized antigen challenge of sensitized mice, and during the host response to infection with Nippostrongylus brasiliensis. These data indicate that MCP-5 is a novel and potent monocyte active chemokine that is involved in allergic inflammation and the host response to pathogens.