tbuckley/cabot-search huggingface dataset:
A randomised, prospective, phase III clinical trial of primary bleomycin, ifosfamide and cisplatin (BIP) chemotherapy followed by radiotherapy versus radiotherapy alone in inoperable cancer of the cervix
Authors: J. Herod, A. Burton, J. Buxton, J. Tobias, D. Luesley, S. Jordan, J. Dunn, C.J. Poole
Journal: Annals of Oncology (2000)
Hospital Variation and Risk Factors for Bronchopulmonary Dysplasia in a Population-Based Cohort
Authors: Wannasiri Lapcharoensap, Susan C. Gage, Peiyi Kan, Jochen Profit, Gary M. Shaw, Jeffrey B. Gould, David K. Stevenson, Hugh O’Brodovich, Henry C. Lee
Journal: JAMA Pediatrics (2015)

IMPORTANCE Bronchopulmonary dysplasia (BPD) remains a serious morbidity in very low-birth-weight (VLBW) infants (<1500 g).Deregionalization of neonatal care has resulted in an increasing number of VLBW infants treated in community hospitals with unknown impact on the development of BPD.OBJECTIVE To identify individual risk factors for BPD development and hospital variation of BPD rates across all levels of neonatal intensive care units (NICUs) within the California Perinatal Quality Care Collaborative.DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study (January 2007 to December 2011) from the California Perinatal Quality Care Collaborative including more than 90% of California's NICUs.Eligible VLBW infants born between 22 to 29 weeks' gestational age.EXPOSURES Varying levels of intensive care.MAIN OUTCOMES AND MEASURES Bronchopulmonary dysplasia was defined as continuous supplemental oxygen use at 36 weeks' postmenstrual age.A combined outcome of BPD or mortality prior to 36 weeks was used.Multivariable logistic regression accounting for hospital as a random effect and gestational age as a risk factor was used to assess individual risk factors for BPD.This model was applied to determine risk-adjusted rates of BPD across hospitals and assess associations between levels of care and BPD rates. RESULTSThe study cohort included 15 779 infants, of which 1534 infants died prior to 36 weeks' postmenstrual age.A total of 7081 infants, or 44.8%, met the primary outcome of BPD or death prior to 36 weeks.Combined BPD or death rates across 116 NICUs varied from 17.7% to 73.4% (interquartile range, 38.7%-54.1%).Compared with level IV NICUs, the risk for developing BPD was higher for level II NICUs (odds ratio, 1.23; 95% CI, 1.02-1.49)and similar for level III NICUs (odds ratio, 1.04; 95% CI, 0.95-1.14).CONCLUSIONS AND RELEVANCE Bronchopulmonary dysplasia or death prior to 36 weeks' postmenstrual age affects approximately 45% of VLBW infants across California.The wide variability in BPD occurrence across hospitals could offer insights into potential risk or preventive factors.Additionally, our findings suggest that increased regionalization of NICU care may reduce BPD among VLBW infants.
The Influence of Language Upon Symptomatology in Foreign-Born Patients
Authors: JULIO C. DEL CASTILLO
Journal: American Journal of Psychiatry (1970)

The author describes several cases in which patients showed psychotic symptoms in interviews held in their native languages but not in those conducted in foreign languages, possibly because the effort of communicating in another tongue produces unconscious vigilance over the emotions. While he does not offer a hypothesis, he suggests that further research in the area of psychiatry and linguistics would be rewarding.
A QUANTITATIVE STUDY OF THE STIMULATION OF DNA SYNTHESIS IN LYMPH NODE CELL CULTURES BY ANTI-LYMPHOCYTE SERUM, ANTI-GAMMA GLOBULIN SERUM, SPECIFIC ANTIGEN, AND PHYTOHEMAGGLUTININ
Authors: John Foerster, Jean-Pierre Lamelin, Ira Green, Baruj Benacerraf
Journal: The Journal of Experimental Medicine (1969)

Rabbit anti-guinea pig lymphocyte serum is an efficient stimulus of the synthesis of DNA by guinea pig lymph node cells in vitro. The ability of ALS to stimulate lymphocytes is characterized by its lack of dependence on prior sensitization, the magnitude of the response it elicits, and the stimulation of all sensitive lymph node cells simultaneously within a very narrow range of ALS concentrations. In contrast to this homogeneous response to ALS, the stimulation of lymph node cells by antigen proceeds in graded fashion over a wide range of concentrations, thus reflecting the heterogeneity of the response of sensitized cells to antigen. PHA gives a response which is intermediate between that of ALS and antigen. ALS appears to have specificity for membrane determinants shared by lymphocytes but not found on other tissues. This specificity does not involve cell-bound gamma globulin. The serum activity mediating lymphocyte stimulation as well as cytotoxicity is readily removed by absorption with lymph node cells.
Chronic lupus peritonitis with ascites.
Authors: P Kaklamanis, G Vayopoulos, G Stamatelos, G Dadinas, G C Tsokos
Journal: Annals of the Rheumatic Diseases (1991)

A 28 year old woman with systemic lupus erythematosus who developed chronic lupus peritonitis and ascites is described. Lupus peritonitis appeared with abdominal fullness, postprandial abdominal discomfort, and painless ascites. Four months later the patient developed vertigo, headaches, visual disturbances, serositis, and glomerulonephritis. Lupus peritonitis and the other disease manifestations responded to treatment with intravenous pulse methylprednisolone (four 1 g/m2 injections at one week intervals), oral azathioprine (200 mg daily), and diuretics.
Maternal Influenza Immunization and Reduced Likelihood of Prematurity and Small for Gestational Age Births: A Retrospective Cohort Study
Authors: Saad B. Omer, David Goodman, Mark C. Steinhoff, Roger Rochat, Keith P. Klugman, Barbara J. Stoll, Usha Ramakrishnan
Journal: PLoS Medicine (2011)

Infections during pregnancy have the potential to adversely impact birth outcomes. We evaluated the association between receipt of inactivated influenza vaccine during pregnancy and prematurity and small for gestational age (SGA) births.We conducted a cohort analysis of surveillance data from the Georgia (United States) Pregnancy Risk Assessment Monitoring System. Among 4,326 live births between 1 June 2004 and 30 September 2006, maternal influenza vaccine information was available for 4,168 (96.3%). The primary intervention evaluated in this study was receipt of influenza vaccine during any trimester of pregnancy. The main outcome measures were prematurity (gestational age at birth <37 wk) and SGA (birth weight <10th percentile for gestational age). Infants who were born during the putative influenza season (1 October-31 May) and whose mothers were vaccinated against influenza during pregnancy were less likely to be premature compared to infants of unvaccinated mothers born in the same period (adjusted odds ratio [OR] = 0.60; 95% CI, 0.38-0.94). The magnitude of association between maternal influenza vaccine receipt and reduced likelihood of prematurity increased during the period of at least local influenza activity (adjusted OR = 0.44; 95% CI, 0.26-0.73) and was greatest during the widespread influenza activity period (adjusted OR = 0.28; 95% CI, 0.11-0.74). Compared with newborns of unvaccinated women, newborns of vaccinated mothers had 69% lower odds of being SGA (adjusted OR = 0.31; 95% CI, 0.13-0.75) during the period of widespread influenza activity. The adjusted and unadjusted ORs were not significant for the pre-influenza activity period.This study demonstrates an association between immunization with the inactivated influenza vaccine during pregnancy and reduced likelihood of prematurity during local, regional, and widespread influenza activity periods. However, no associations were found for the pre-influenza activity period. Moreover, during the period of widespread influenza activity there was an association between maternal receipt of influenza vaccine and reduced likelihood of SGA birth.
Phylogenetic analysis of the human basic helix-loop-helix proteins
Authors: Valérie Ledent, Odier Paquet, Michel Vervoort
Journal: Genome biology (2002)

The basic helix-loop-helix (bHLH) proteins are a large and complex multigene family of transcription factors with important roles in animal development, including that of fruitflies, nematodes and vertebrates. The identification of orthologous relationships among the bHLH genes from these widely divergent taxa allows reconstruction of the putative complement of bHLH genes present in the genome of their last common ancestor. We identified 39 different bHLH genes in the worm Caenorhabditis elegans, 58 in the fly Drosophila melanogaster and 125 in human (Homo sapiens). We defined 44 orthologous families that include most of these bHLH genes. Of these, 43 include both human and fly and/or worm genes, indicating that genes from these families were already present in the last common ancestor of worm, fly and human. Only two families contain both yeast and animal genes, and no family contains both plant and animal bHLH genes. We suggest that the diversification of bHLH genes is directly linked to the acquisition of multicellularity, and that important diversification of the bHLH repertoire occurred independently in animals and plants. As the last common ancestor of worm, fly and human is also that of all bilaterian animals, our analysis indicates that this ancient ancestor must have possessed at least 43 different types of bHLH, highlighting its genomic complexity.
Endogenous RGS Proteins and Gα Subtypes Differentially Control Muscarinic and Adenosine-Mediated Chronotropic Effects
Authors: Ying Fu, Xinyan Huang, Huailing Zhong, Richard M. Mortensen, Louis G. D’Alecy, Richard R. Neubig
Journal: Circulation Research (2006)

Cardiac automaticity is controlled by G protein-coupled receptors, such as adrenergic, muscarinic, and adenosine receptors. The strength and duration of G protein signaling is attenuated by regulator of G protein signaling (RGS) proteins acting as GTPase-activating proteins for Galpha subunits; however, little is known about the role of endogenous RGS proteins in cardiac function. We created point mutations in Galpha subunits that disrupt Galpha-RGS binding and introduced them into embryonic stem (ES) cells by homologous recombination. Spontaneously contacting cardiocytes derived from the ES cells were used to evaluate the role of endogenous RGS proteins in chronotropic regulation. The RGS-insensitive GalphaoG184S homozygous knock-in (GalphaoGS/GS) cells demonstrated enhanced adenosine A1 and muscarinic M2 receptor-mediated bradycardic responses. In contrast, Galphai2GS/GS cells showed enhanced responses to M2 but not A1 receptors. Similarly M2 but not A1 bradycardic responses were dramatically enhanced in Galphai2GS/GS mice. Blocking G protein-coupled inward rectifying K+ (GIRK) channels largely abolished the mutation-induced enhancement of the M2 receptor-mediated response but had a minimal effect on A1 responses. The Galphas-dependent stimulation of beating rate by the beta2 adrenergic receptor agonist procaterol was significantly attenuated in GalphaoGS/GS and nearly abolished in Galphai2GS/GS cells because of enhanced signaling via a pertussis toxin sensitive mechanism. Thus, endogenous RGS proteins potently reduce the actions of Galpha(i/o)-linked receptors on cardiac automaticity. Furthermore, M2 and A1 receptors differentially use Galphai2 and Galphao and associated downstream effectors. Thus, alterations in RGS function may play a role in pathophysiological processes and RGS proteins could represent novel cardiovascular therapeutic targets.
Tissue-Specific Patterns of Gap Junctions in Adult Rat Atrial and Ventricular Cardiomyocytes In Vivo and In Vitro
Authors: Sawa Kostin, Jutta Schaper
Journal: Circulation Research (2001)

To verify the hypothesis that tissue-specific patterns of gap junctions (GJs) are determined by intrinsic factors within myocytes forming different cardiac tissues, we have compared by quantitative transmission electron microscopy (TEM) the structural features of GJs in adult rat atrial myocytes (AMs) and ventricular myocytes (VMs) in vivo with those in developing GJs in cultured AMs and VMs in vitro. Quantitative TEM data revealed a 3-fold increase in the number of developing GJs per intercalated disk in both AMs and VMs from 6 to 15 days in culture. However, at days 12 and 15, the percentage of GJ length per intercalated disk and mean GJ length were 2-fold higher in VMs than in AMS: Measurements of connexin43 GJs by confocal microscopy confirmed TEM data and demonstrated respectively 2- and 4.5-fold greater mean values of GJ length and area in VMs than in AMS: These differences are attributable to the development of large GJs (>3 micrometer) in VMs, closely resembling those observed in VMs in vivo. Although large GJs in cultured VMs comprised approximately 14% of the total number of GJs, their contribution to total GJ length and area constituted >60% and 85%, respectively. In marked contrast, the number of large GJs in AMs both in vitro and in vivo was <1% from the total number of GJS: These data confirm our hypothesis and provide the first evidence that tissue-specific patterns of GJs in AMs and VMs are determined primarily by intrinsic factors within cardiac myocytes and are developmentally regulated.
Serotonin Is Associated with Coronary Artery Disease and Cardiac Events
Authors: Kjell Vikenes, Mikael Farstad, Jan Erik Nordrehaug
Journal: Circulation (1999)

Blood platelets are related to coronary atherogenesis. Platelets secrete serotonin (5-hydroxytryptamine) which has several effects on the vascular wall and promotes thrombogenesis, mitogenesis, and proliferation of smooth muscle cells. Serotonin may therefore be one of the factors involved in the development of coronary artery disease (CAD). We have assessed serotonin among conventional predictors for CAD in patients undergoing coronary angiography for chest pain or clinically suspected angina pectoris.Of 121 consecutive male patients (mean age 65, range 41 to 90 years) undergoing angiography, 96 had coronary artery stenosis and 25 had normal angiograms. Serotonin, blood platelet count, and conventional biochemical risk factors for CAD were determined in the morning the day before the angiography. High serotonin (cut-point 1000 nmol/L) was significantly associated with CAD with an odds ratio (OR) of 3.4 (95% confidence interval 1.2 to 9. 8). The corresponding OR for smokers was 4.8 (1.9 to 12.2); hypercholesterolemia (>7 mmol/L), 2.9 (1.1 to 7.6); high platelet count (cut-point 325 10(9)/L), 3.0 (1.0 to 9.5); and family history of heart disease, 2.3 (1.0 to 5.2). After adjustment with conventional risk factors, the OR for CAD was 3.8 (1.1 to 13.1), comparing high and low values of serotonin. The relation between serotonin and CAD was strengthened only when patients <70 years (n=82) were included in the analysis. In this age group, the occurrence of cardiac events during a mean of 3.7 years of follow-up was significantly associated with high serotonin values.The study suggests that serotonin is associated with coronary artery disease and occurrence of cardiac events, particularly in younger age groups. This association seems to persist after adjustment for conventional risk factors.
The Fate of Mutations Surfing on the Wave of a Range Expansion
Authors: Seraina Klopfstein, Mathias Currat, Laurent Excoffier
Journal: Molecular Biology and Evolution (2005)

Many species, including humans, have dramatically expanded their range in the past, and such range expansions had certainly an impact on their genetic diversity. For example, mutations arising in populations at the edge of a range expansion can sometimes surf on the wave of advance and thus reach a larger spatial distribution and a much higher frequency than would be expected in stationary populations. We study here this surfing phenomenon in more detail, by performing extensive computer simulations under a two-dimensional stepping-stone model. We find that the probability of survival of a new mutation depends to a large degree on its proximity to the edge of the wave. Demographic factors such as deme size, migration rate, and local growth rate also influence the fate of these new mutations. We also find that the final spatial and frequency distributions depend on the local deme size of a subdivided population. This latter result is discussed in the light of human expansions in Europe as it should allow one to distinguish between mutations having spread with Paleolithic or Neolithic expansions. By favoring the spread of new mutations, a consequence of the surfing phenomenon is to increase the rate of evolution of spatially expanding populations.
Defective removal of ribonucleotides from DNA promotes systemic autoimmunity
Authors: Claudia Günther, Barbara Kind, Martin A.M. Reijns, Nicole Berndt, Manuel Martinez-Bueno, Christine Wolf, Victoria Tüngler, Osvaldo Chara, Young Ae Lee, Norbert Hübner, Louise Bicknell, Sophia Blum, Claudia Krug, Franziska Schmidt, Stefanie Kretschmer, Sarah Koss, Katy R. Astell, Georgia Ramantani, Anja Bauerfeind, David L. Morris, Deborah S. Cunninghame Graham, Doryen Bubeck, Andrea Leitch, Stuart H. Ralston, Elizabeth A. Blackburn, Manfred Gahr, Torsten Witte, Timothy J. Vyse, Inga Melchers, Elisabeth Mangold, Markus M. Nöthen, Martin Aringer, Annegret Kuhn, Kirsten Lüthke, Leonore Unger, Annette Bley, Alice Lorenzi, John D. Isaacs, Dimitra Alexopoulou, Karsten Conrad, Andreas Dahl, Axel Roers, Marta E. Alarcon-Riquelme, Andrew P. Jackson, Min Ae Lee-Kirsch
Journal: Journal of Clinical Investigation (2014)

Genome integrity is continuously challenged by the DNA damage that arises during normal cell metabolism. Biallelic mutations in the genes encoding the genome surveillance enzyme ribonuclease H2 (RNase H2) cause Aicardi-Goutières syndrome (AGS), a pediatric disorder that shares features with the autoimmune disease systemic lupus erythematosus (SLE). Here we determined that heterozygous parents of AGS patients exhibit an intermediate autoimmune phenotype and demonstrated a genetic association between rare RNASEH2 sequence variants and SLE. Evaluation of patient cells revealed that SLE- and AGS-associated mutations impair RNase H2 function and result in accumulation of ribonucleotides in genomic DNA. The ensuing chronic low level of DNA damage triggered a DNA damage response characterized by constitutive p53 phosphorylation and senescence. Patient fibroblasts exhibited constitutive upregulation of IFN-stimulated genes and an enhanced type I IFN response to the immunostimulatory nucleic acid polyinosinic:polycytidylic acid and UV light irradiation, linking RNase H2 deficiency to potentiation of innate immune signaling. Moreover, UV-induced cyclobutane pyrimidine dimer formation was markedly enhanced in ribonucleotide-containing DNA, providing a mechanism for photosensitivity in RNase H2-associated SLE. Collectively, our findings implicate RNase H2 in the pathogenesis of SLE and suggest a role of DNA damage-associated pathways in the initiation of autoimmunity.
Evolution of duplicate genes in a tetraploid animal, Xenopus laevis.
Authors: M K Hughes, A L Hughes
Journal: Molecular Biology and Evolution (1993)

To understand the evolution of duplicate genes, we compared rates of nucleotide substitution between 17 pairs of nonallelic duplicated genes in the tetraploid frog Xenopus laevis with rates between the orthologous loci of human and rodent. For all duplicated X. laevis genes, the number of synonymous substitutions per site (dS) was greater than the number of nonsynonymous substitutions per site (dN), indicating that these genes are subject to purifying selection. There was also a significant positive correlation (r = 0.915) between dN for the X. laevis genes and dN for the mammalian genes, suggesting that, at the amino acid level, the X. laevis genes and the mammalian genes are under similar constraints. Results of relative-rate tests showed nearly equal rates of nonsynonymous substitution in each copy of the X. laevis genes; apparently there are similar constraints on both copies. No correlation was found between dS for the X. laevis genes and dS for the mammalian genes. There was a significant positive correlation both between members of pairs of duplicated X. laevis genes (r = 0.951) and between human and rodent orthologues (r = 0.854) with respect to third-position G+C content but no such relationship between the X. laevis genes and either of their mammalian orthologues. The results indicate that both copies of a duplicate gene can be subject to purifying selection and thus support the hypothesis of selection against all genotypes containing a null allele at either of two duplicate loci.
Multicenter non-randomized phase II study of raltitrexed (Tomudex) and oxaliplatin in non-pretreated metastatic colorectal cancer patients
Authors: J.-F. Seitz, J. Bennouna, B. Paillot, E. Gamelin, E. François, T. Conroy, J.-L. Raoul, Y. Becouarn, F. Bertheault-Cvitkovic, M. Ychou, S. Nasca, A. Fandi, P. Barthelemy, J.-Y. Douillard
Journal: Annals of Oncology (2002)
Study Supports PSA Velocity Risk Count
Authors: M. Fillon
Journal: JNCI Journal of the National Cancer Institute (2012)

mid ongoing controversy on the value of prostate-specific antigen (PSA) screening, a slightly different measure-PSA velocity (PSAV) "risk count," the number of times a patient exceeds a PSAV threshold-may offer a more effective way for physicians to screen men for clinically meaningful prostate cancer than PSA alone.Many researchers have disagreed over whether PSAV-increases in PSA level over time-is a good indicator of prostate cancer and grounds for a prostate biopsy.The new PSAV risk count screening monitors and quantifies fluctuations in PSA levels.Under this method, the risk count is calculated by counting how many consecutive times the PSA level in the blood increases by 0.4 ng/ mL.If PSA goes up by more than 0.4 unit for several years in a row, the risk count rises, indicating an increased risk of aggressive prostate cancer.