tbuckley/cabot-search huggingface dataset:
Prostanoid signal transduction and gene expression in the endothelium: Role in cardiovascular diseases
Authors: A ALFRANCA, M INIGUEZ, M FRESNO, J REDONDO
Journal: Cardiovascular Research (2006)

Endothelial cells play an active role in the maintenance of homeostasis. Endothelial injury can give rise to endothelial dysfunction in which the profile of mediators released by endothelial cells is altered. Among these mediators are factors that participate in the development of many cardiovascular disorders. Some of the most important are the prostanoids, which can modulate the progression of atherosclerosis, arterial hypertension, and angiogenesis. Prostanoids are produced by the sequential actions of cyclooxygenases and specific synthases and exert their actions through diverse cell-surface and nuclear receptors. The profile of prostanoids produced depends on cell type and the changing pathophysiological status, and these factors similarly affect the great array of biological responses elicited by these molecules. The resulting complexity enables extremely subtle and highly complex responses, and this provides opportunities for the development of targeted therapeutic approaches.
Patterns and Outcomes of Red Blood Cell Transfusion in Patients Undergoing Percutaneous Coronary Intervention
Authors: Matthew W. Sherwood, Yongfei Wang, Jeptha P. Curtis, Eric D. Peterson, Sunil V. Rao
Journal: JAMA (2014)

Studies have shown variation in the use of red blood cell transfusion among patients with acute coronary syndromes. There are no definitive data for the efficacy of transfusion in improving outcomes, and concerning data exist about possible association with harm. Current transfusion practices in patients undergoing percutaneous coronary intervention (PCI) are not well understood.To determine the current patterns of blood transfusion among patients undergoing PCI and the association of transfusion with adverse cardiac outcomes across hospitals in the United States.Retrospective cohort study of all patient visits from the CathPCI Registry from July 2009 to March 2013 that included PCI, excluding those with missing data on bleeding complications or who underwent in-hospital coronary artery bypass graft surgery (N = 2,258,711 visits).Transfusion rates in the overall population and by hospital (N = 1431) were the primary outcomes. The association of transfusion with myocardial infarction, stroke, and death after accounting for a patient's propensity for transfusion was also measured.The overall rate of transfusion was 2.14% (95% CI, 2.13%-2.16%) and quarterly transfusion rates slightly declined from July 2009 to March 2013 (from 2.11% [95% CI, 2.03%-2.19%] to 2.04% [95% CI, 1.97%-2.12%]; P < .001). Patients who were more likely to receive transfusion were older (mean, 70.5 vs 64.6 years), were women (56.3% vs 32.5%), and had hypertension (86.4% vs 82.0%), diabetes (44.8% vs 34.6%), advanced renal dysfunction (8.7% vs 2.3%), prior myocardial infarction (33.0% vs 30.2%), or prior heart failure (27.0% vs 11.8%). Overall, 96.3% of sites gave a transfusion to less than 5% of patients and 3.7% of sites gave a transfusion to 5% of patients or more. Variation in hospital risk-standardized rates of transfusion persisted after adjustment, and hospitals showed variability in their transfusion thresholds. Receipt of transfusion was associated with myocardial infarction (42,803 events; 4.5% vs 1.8%; odds ratio [OR], 2.60; 95% CI, 2.57-2.63), stroke (5011 events; 2.0% vs 0.2%; OR, 7.72; 95% CI, 7.47-7.98), and in-hospital death (31,885 events; 12.5% vs 1.2%; OR, 4.63; 95% CI, 4.57-4.69), irrespective of bleeding complications.Among patients undergoing PCI at US hospitals, there was considerable variation in blood transfusion practices, and receipt of transfusion was associated with increased risk of in-hospital adverse cardiac events. These observational findings may warrant a randomized trial of transfusion strategies for patients undergoing PCI.
Spirometry in healthy men: a correlation with smoking and with mild symptoms.
Authors: F Prieto, M J English, G M Cochrane, T J Clark, B G Rigden
Journal: Thorax (1978)

Spirometry in healthy men: a correlation with smoking and with mild symptoms.Symptoms, smoking history, and variates taken from the forced expiratory manoeuvre were studied in a group of 271 healthy men attending a mass radiography unit.It was found that correlation of the forced expiratory ratio (FEV,/FVC) with the presence of mild or moderate respiratory symptoms was at least as satisfactory as that of technically more complicated measurements such as MEF,o and MEF75.In asymptomatic individuals those differences associated with smoking were the same for FEV,/FVC as for MEF75.Asymptomatic abnormalities of lung function were not observed.Simple measurements such as FEV1/FVC can therefore provide as much information from a forced expiratory manoeuvre to screen for early airways obstruction as MEF50 and MEF75.
P1238 SVR24 RATE OF 60% IN HCV G1-INFECTED PRIOR NULL RESPONDERS TREATED WITH MERICITABINE (MCB), BOCEPREVIR (BOC) PLUS PEGIFN ALFA-2a/RIBAVIRIN (P/R): RESULTS FROM DYNAMO 1
Authors: H. Wedemeyer, C. Hézode, S.S. Lee, A. Scalori, S. Zhao, A. Voulgari, J. Thommes
Journal: Journal of Hepatology (2014)
Reproducibility of transient elastography in the evaluation of liver fibrosis in patients with chronic liver disease
Authors: M. Fraquelli, C. Rigamonti, G. Casazza, D. Conte, M. F. Donato, G. Ronchi, M. Colombo
Journal: Gut (2007)

<h3>Background</h3> The molecular genetic basis of pulmonary arterial hypertension (PAH) is heterogeneous, with at least 26 genes displaying putative evidence for disease causality. Heterozygous variants in the <i>ATP13A3</i> gene were recently identified as a new cause of adult-onset PAH. However, the contribution of <i>ATP13A3</i> risk alleles to child-onset PAH remains largely unexplored. <h3>Methods and results</h3> We report three families with a novel, autosomal recessive form of childhood-onset PAH due to biallelic <i>ATP13A3</i> variants. Disease onset ranged from birth to 2.5 years and was characterised by high mortality. Using genome sequencing of parent–offspring trios, we identified a homozygous missense variant in one case, which was subsequently confirmed to cosegregate with disease in an affected sibling. Independently, compound heterozygous variants in <i>ATP13A3</i> were identified in two affected siblings and in an unrelated third family. The variants included three loss of function variants (two frameshift, one nonsense) and two highly conserved missense substitutions located in the catalytic phosphorylation domain. The children were largely refractory to treatment and four died in early childhood. All parents were heterozygous for the variants and asymptomatic. <h3>Conclusion</h3> Our findings support biallelic predicted deleterious <i>ATP13A3</i> variants in autosomal recessive, childhood-onset PAH, indicating likely semidominant dose-dependent inheritance for this gene.
PET Study of D<sub>1</sub> Dopamine Receptor Binding in Neuroleptic-Naive Patients With Schizophrenia
Authors: Per Karlsson, Lars Farde, Christer Halldin, Göran Sedvall
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Postmortem studies and a positron emission tomography (PET) study have suggested that there is a disturbance of central D1 dopamine receptor function in schizophrenia. The objective of the present PET study was to compare D1 receptor binding in first-admission, neuroleptic-naive patients with schizophrenia and in healthy subjects. METHOD: Ten healthy comparison subjects and 10 neuroleptic-naive patients with schizophrenia (diagnosed according to DSM-III-R) were examined twice by PET using 11C-labeled SCH 23390 ([11C]SCH 23390) with high and low specific radioactivity, respectively. The binding potential, receptor density (Bmax), and affinity (Kd) were determined for the caudate nucleus, the putamen, and several neocortical regions during both PET examinations. Scatchard plots from the two measurements were used to calculate regional D1 Bmax and Kd. The regional binding values were tested for hemispheric asymmetry and for correlation to clinical symptoms measured by the Brief Psychiatric Rating Scale (BPRS). RESULTS: [11C]SCH 23390 binding to D1 receptors did not differ significantly between subjects with schizophrenia and healthy subjects in any of the brain regions or for any of the binding measures studied. Asymmetry of the regional binding values did not differ significantly between the two groups. Scores on the BPRS negative symptom subscale correlated significantly with the Bmax in the right frontal cortex. CONCLUSIONS: These results do not replicate previous postmortem and PET findings of altered central dopamine D1 receptor binding in schizophrenia. The finding of a positive correlation between frontal D1 binding and scores on the negative symptom subscale of the BPRS is contrary to a previously reported finding of a negative correlation. These discrepancies motivate further studies using D1 ligands with higher signals for cortical regions.
Phase 2 study of safety and efficacy of nimotuzumab in pediatric patients with progressive diffuse intrinsic pontine glioma
Authors: U. Bartels, J. Wolff, L. Gore, I. Dunkel, S. Gilheeney, J. Allen, S. Goldman, M. Yalon, R. J. Packer, D. N. Korones, A. Smith, K. Cohen, J. Kuttesch, D. Strother, S. Baruchel, J. Gammon, M. Kowalski, E. Bouffet
Journal: Neuro-Oncology (2014)

The prognosis of diffuse intrinsic pontine glioma (DIPG) remains poor, with no drug proven to be effective. Patients with clinically and radiologically confirmed, centrally reviewed DIPG, who had failed standard first-line therapy were eligible for this multicenter phase II trial. The anti-epidermal growth factor receptor (EGFR) antibody, nimotuzumab (150 mg/m2), was administered intravenously once weekly from weeks 1 to 7 and once every 2 weeks from weeks 8 to 18. Response evaluation was based on clinical and MRI assessments. Patients with partial response (PR) or stable disease (SD) were allowed to continue nimotuzumab. Forty-four patients received at least one dose of nimotuzumab (male/female, 20/24; median age, 6.0 years; range, 3.0–17.0 years). All had received prior radiotherapy. Treatment was well tolerated. Eighteen children experienced serious adverse events (SAEs). The majority of SAEs were associated with disease progression. Nineteen patients completed 8 weeks (W8) of treatment: There were 2 PRs, 6 SDs, and 11 progressions. Five patients completed 18 weeks (W18) of treatment: 1 of 2 patients with PR at W8 remained in PR at W18, and 3 of 6 children with SD at W8 maintained SD at W18. Time to progression following initiation of nimotuzumab for the 4 patients with SD or better at W18 was 119, 157, 182 and 335 days, respectively. Median survival time was 3.2 months. Two patients lived 663 and 481 days from the start of nimotuzumab. Modest activity of nimotuzumab in DIPG, which has been shown previously, was confirmed: A small subset of DIPG patients appeared to benefit from anti-EGFR antibody treatment.
Data Withholding in Academic Genetics
Authors: Eric G. Campbell, Brian R. Clarridge, Manjusha Gokhale, Lauren Birenbaum, Stephen Hilgartner, Neil A. Holtzman, David Blumenthal
Journal: JAMA (2002)

ContextThe free and open sharing of information, data, and materials regarding published research is vital to the replication of published results, the efficient advancement of science, and the education of students. Yet in daily practice, the ideal of free sharing is often breached.ObjectiveTo understand the nature, extent, and consequences of data withholding in academic genetics.Design, Setting, and ParticipantsMailed survey (March-July 2000) of geneticists and other life scientists in the 100 US universities that received the most funding from the National Institutes of Health in 1998. Of a potential 3000 respondents, 2893 were eligible and 1849 responded, yielding an overall response rate of 64%. We analyzed a subsample of 1240 self-identified geneticists and made a limited number of comparisons with 600 self-identified nongeneticists.Main Outcome MeasuresPercentage of faculty who made requests for data that were denied; percentage of respondents who denied requests; influences on and consequences of withholding data; and changes over time in perceived willingness to share data.ResultsForty-seven percent of geneticists who asked other faculty for additional information, data, or materials regarding published research reported that at least 1 of their requests had been denied in the preceding 3 years. Ten percent of all postpublication requests for additional information were denied. Because they were denied access to data, 28% of geneticists reported that they had been unable to confirm published research. Twelve percent said that in the previous 3 years, they had denied another academician's request for data concerning published results. Among geneticists who said they had intentionally withheld data regarding their published work, 80% reported that it required too much effort to produce the materials or information; 64%, that they were protecting the ability of a graduate student, postdoctoral fellow, or junior faculty member to publish; and 53%, that they were protecting their own ability to publish. Thirty-five percent of geneticists said that sharing had decreased during the last decade; 14%, that sharing had increased. Geneticists were as likely as other life scientists to deny others' requests (odds ratio [OR], 1.39; 95% confidence interval [CI], 0.81-2.40) and to have their own requests denied (OR, 0.97; 95% CI, 0.69-1.40). However, other life scientists were less likely to report that withholding had a negative impact on their own research as well as their field of research.ConclusionsData withholding occurs in academic genetics and it affects essential scientific activities such as the ability to confirm published results. Lack of resources and issues of scientific priority may play an important role in scientists' decisions to withhold data, materials, and information from other academic geneticists.
Paraumbilical vein patency in cirrhosis: Effects on hepatic hemodynamics evaluated by doppler sonography
Authors: David Sacerdoti, Massimo Bolognesi, Giancarlo Bombonato, Angelo Gatta
Journal: Hepatology (1995)

Doppler sonographic portal vein parameters are used for the noninvasive evaluation of portal hypertension in cirrhosis. The patency of a paraumbilical vein is a rather frequent finding in cirrhosis, which may affect hepatic hemodynamics and function. We evaluated portal and hepatic arterial parameters in 184 cirrhotic patients with and without a patent paraumbilical vein and the relationships with paraumbilical blood flow. A patent paraumbilical vein was found in 33.7% of patients. The prevalence was higher (56.8%) in Child C patients. Portal blood flow velocity (PBV) (10.8 +/- 2.2 vs. 9.8 +/- 2.4 cm/sec; P < .01) and volume (PBF) (995.0 +/- 383.8 vs. 811.6 +/- 318.7 mL/min; P < .001) was significantly higher, and effective portal liver perfusion (PLP) (portal blood flow--paraumbilical blood flow) (621.3 +/- 420.8 vs. 811.6 +/- 318.7 mL/min; P < .001) was significantly lower in patients with a patent paraumbilical vein than in those without. These differences were more evident in Child C patients (10.7 +/- 2.0 vs. 8.3 +/- 2.3 cm/sec; 935.7 +/- 378.3 vs. 680.6 +/- 239.4 mL/min; 369.0 +/- 282.0 vs. 680.6 +/- 239.4 mL/min). Portal vein diameter, the congestion index (CI) of the portal vein, hepatic arterial resistance indexes, and the severity of esophageal varices did not differ between the two groups. In patients with a patent paraumbilical vein, the Child-Pugh score and the prevalence of ascites were significantly higher than in those without. In conclusion, the evaluation of PBV and PBF in cirrhotic patients can provide misleading results if a paraumbilical vein is patent, underestimating the degree of portal hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
Proapoptotic Activity of Cell-Permeable Anti-Akt Single-Chain Antibodies
Authors: Incheol Shin, Jeniffer Edl, Swati Biswas, P. Charles Lin, Raymond Mernaugh, Carlos L. Arteaga
Journal: Cancer Research (2005)

Abstract We developed anti-Akt1 single-chain antibodies (scFv) by panning a mouse phage–displayed scFv recombinant antibody library. Recombinant scFv that bound glutathione S-transferase (GST)-Akt1 were screened for their ability to inhibit Akt activity in vitro in a kinase reaction containing human recombinant Akt1 and an Akt/serum glucocorticoid-inducible kinase (SGK) substrate. Michaelis-Menten analysis of kinase inhibition by a selected scFv was consistent with scFv-mediated competition with enzyme's substrate for the catalytic site of Akt. To generate a membrane-permeable version of the anti-Akt1 scFv, the scFv gene was subcloned into a GST expression vector carrying a membrane-translocating sequence (MTS) from Kaposi fibroblast growth factor. A purified GST–anti-Akt1–MTS fusion protein accumulated intracellularly in 293T, BT-474, and PyVmT cells in a dose- and time-dependent fashion. Intracellular accumulation correlated temporally with inhibition of p-Ser473 Akt and GSK-3α/β phosphorylation, suggesting that Ser473 is an Akt autophosphorylation site. Phosphorylated (activated) phosphoinositide-dependent kinase 1, mitogen-activated protein kinase, p38, and HER2 (erbB2) were not affected, supporting Akt kinase specificity for the inhibitory scFv. Exogenously expressed constitutively active Akt2 and Akt3 were also inhibited in vitro by the anti-Akt1 fusion protein. Furthermore, GST–anti-Akt1–MTS induced apoptosis in three cancer cell lines that express constitutively active Akt. Finally, systemic treatment with the anti-Akt scFv reduced tumor volume and neovascularization and increased apoptosis in PyVmT-expressing transgenic tumors implanted in mouse dorsal window chambers. Thus, GST–anti-Akt1–MTS is a novel cell-permeable inhibitor of Akt, which selectively inhibits Akt-mediated survival in intact cells both in vitro and in vivo.
Running economy in early and late maturing youth soccer players does not differ
Authors: V Segers, D De Clercq, M Janssens, J Bourgois, R Philippaerts
Journal: British Journal of Sports Medicine (2008)

The aim of this study was to investigate the influence of maturity on running economy in a population of young soccer players.13 boys (mean age 14.3 years) active in soccer were divided into two groups: 6 early and 7 late maturers. Anthropometrical characteristics, respiratory exchange ratio, heart rate and maximal oxygen uptake were measured. Running economy was assessed at three submaximal running speeds (8, 9.5 and 11 km/h). Allometric coefficients were calculated and used to diminish the effect of body mass. In addition, running style was analysed biomechanically (stride length and meaningful kinematic values).There was no significant difference in the running economy of early and late maturing soccer players, nor any significant differences in mass adjusted physiological values. Therefore physiological differences cannot explain why late maturers succeed in keeping up with early maturers. Late maturing boys take longer relative strides, and have more anteversion of the thigh at heel contact, a smaller knee-angle during swing-phase and a lower mass moment of inertia.Running style seems to be an important determinant in running economy of children.
Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix
Authors: Basak E Uygun, Alejandro Soto-Gutierrez, Hiroshi Yagi, Maria-Louisa Izamis, Maria A Guzzardi, Carley Shulman, Jack Milwid, Naoya Kobayashi, Arno Tilles, Francois Berthiaume, Martin Hertl, Yaakov Nahmias, Martin L Yarmush, Korkut Uygun
Journal: Nature Medicine (2010)
Insertion of <i>Myc</i> into <i>Igh</i> Accelerates Peritoneal Plasmacytomas in Mice
Authors: Sung Sup Park, Arthur L. Shaffer, Joong Su Kim, Wendy duBois, Michael Potter, Louis M. Staudt, Siegfried Janz
Journal: Cancer Research (2005)

Gene-targeted mice that contain a His6-tagged mouse c-Myc cDNA, Myc(His), inserted head to head into different sites of the mouse immunoglobulin heavy-chain locus, Igh, mimic the chromosomal T(12;15)(Igh-Myc) translocation that results in the activation of Myc in the great majority of mouse plasmacytomas. Mice carrying Myc(His) just 5' of the intronic heavy-chain enhancer Emu (strain iMyc(Emu)) provide a specific model of the type of T(12;15) found in a subset (approximately 20%) of plasmacytomas that develop "spontaneously" in the gut-associated lymphoid tissue (GALT) of interleukin-6 transgenic BALB/c (C) mice. Here we show that the transfer of the iMyc(Emu) transgene from a mixed genetic background of segregating C57BL/6 x 129/SvJ alleles to the background of C increased the incidence of GALT plasmacytomas by a factor of 2.5 in first-generation backcross mice (C.iMyc(Emu) N1). Third-generation backcross mice (C.iMyc(Emu) N3, approximately 94% C alleles) were hypersusceptible to inflammation-induced peritoneal plasmacytomas (tumor incidence, 100%; mean tumor onset, 86 +/- 28 days) compared with inbred C mice (tumor incidence, 5% on day 150 after tumor induction). Peritoneal plasmacytomas of C.iMyc(Emu) N3 mice overexpressed Myc(His), produced monoclonal immunoglobulin, and exhibited a unique plasma cell signature upon gene expression profiling on mouse Lymphochip cDNA microarrays. These findings indicated that the iMyc(Emu) transgene accelerates plasmacytoma development by collaborating with tumor susceptibility alleles of strain C and circumventing the requirement for tumor precursors to acquire deregulated Myc by chromosomal translocation.
Evolutionary theory and the social sciences
Authors: Robert L. Burgess, Peter C. M. Molenaar
Journal: Behavioral and Brain Sciences (2007)

Gintis's article is an example of growing awareness by social scientists of the significance of evolutionary theory for understanding human nature. Although we share its main point of view, we comment on some disagreements related to levels of behavioral analysis, the explanation of social cooperation, and the ubiquity of inter-individual differences in human decision-making.
Immunotherapy of an Intramuscular Tumor in Strain-2 Guinea Pigs: Prevention of Tumor Growth by Intradermal Immunization and by Systemic Transfer of Tumor Immunity
Authors: Harold T. Wepsic, Barry S. Kronman, Berton Zbar, Tibor Borsos, Herbert J. Rapp
Journal: JNCI Journal of the National Cancer Institute (1970)

Immunotherapy of tumor cells inoculated intramuscularly was accomplished by intradermal immunization with living tumor cells. Immunization with cells of the ascites variant of the same tumor cell line resulted in protection of 27% of the animals, and immunization with tumor cells grown in tissue culture resulted in protection of 50% of the animals. Intradermal immunization with frozen-thawed ascites tumor cells, spleen cells, X-irradiated ascites tumor cells, and with tumor cells antigenically unrelated to the challenge inoculum did not prevent growth of the intramuscular tumor. Immunotherapy with intradermal immunization and with systemic transfer of peritoneal exudate cells was effective only when the tumor mass was relatively small. Systemic transfer of immunized peritoneal exudate cells to a tumor-bearing animal prevented tumor growth in 60% of the animals.