tbuckley/cabot-search huggingface dataset:
Sex ratio and time to pregnancy: analysis of four large European population surveys
Authors: Mike Joffe, James Bennett, Nicky Best, Tina Kold Jensen
Journal: BMJ (2007)

<b>Objective</b> To test whether the secondary sex ratio (proportion of male births) is associated with time to pregnancy, a marker of fertility. <b>Design </b>Analysis of four large population surveys. <b>Setting </b>Denmark and the United Kingdom. <b>Participants </b>49 506 pregnancies. <b>Main outcome measure</b> Secondary sex ratio. <b>Results</b> No association was found between the sex ratio and time to pregnancy and no discernible trend was found for sex ratio with time to pregnancy, either within individual datasets or in the pooled analysis. The odds ratios were 0.97 (95% confidence interval 0.90 to 1.04) for contraceptive failures, 1.01 (0.96 to 1.05) for time to pregnancy of 2-4 months, 1.02 (0.97 to 1.08) for 5-10 months, 0.98 (0.93 to 1.03) for 11 months or more, and 0.88 (0.74 to 1.06) for fertility treatment, with 0-1 months as the reference category. <b>Conclusion</b> No association was found between the secondary sex ratio and time to pregnancy.
Large-scale 13C-flux analysis reveals mechanistic principles of metabolic network robustness to null mutations in yeast.
Authors: Lars M Blank, Lars Kuepfer, Uwe Sauer
Journal: Genome biology (2005)

Abstract Background Quantification of intracellular metabolite fluxes by 13 C-tracer experiments is maturing into a routine higher-throughput analysis. The question now arises as to which mutants should be analyzed. Here we identify key experiments in a systems biology approach with a genome-scale model of Saccharomyces cerevisiae metabolism, thereby reducing the workload for experimental network analyses and functional genomics. Results Genome-scale 13 C flux analysis revealed that about half of the 745 biochemical reactions were active during growth on glucose, but that alternative pathways exist for only 51 gene-encoded reactions with significant flux. These flexible reactions identified in silico are key targets for experimental flux analysis, and we present the first large-scale metabolic flux data for yeast, covering half of these mutants during growth on glucose. The metabolic lesions were often counteracted by flux rerouting, but knockout of cofactor-dependent reactions, as in the adh1 , ald6 , cox5A , fum1 , mdh1 , pda1 , and zwf1 mutations, caused flux responses in more distant parts of the network. By integrating computational analyses, flux data, and physiological phenotypes of all mutants in active reactions, we quantified the relative importance of 'genetic buffering' through alternative pathways and network redundancy through duplicate genes for genetic robustness of the network. Conclusions The apparent dispensability of knockout mutants with metabolic function is explained by gene inactivity under a particular condition in about half of the cases. For the remaining 207 viable mutants of active reactions, network redundancy through duplicate genes was the major (75%) and alternative pathways the minor (25%) molecular mechanism of genetic network robustness in S. cerevisiae .
Growth, phenotype, and function of human intestinal mast cells are tightly regulated by transforming growth factor 1
Authors: T Gebhardt
Journal: Gut (2005)

Transforming growth factor beta1 (TGF-beta1) is expressed in the healthy human intestine and controls mucosal immune responses and inflammation by regulating the function of lymphocytes, macrophages, dendritic cells, and eosinophils. Here, we asked whether human intestinal mast cells (MC) might also be subject to immunoregulation by TGF-beta1.
Discovery of Endothelial to Mesenchymal Transition as a Source for Carcinoma-Associated Fibroblasts
Authors: Elisabeth M. Zeisberg, Scott Potenta, Liang Xie, Michael Zeisberg, Raghu Kalluri
Journal: Cancer Research (2007)

Activated fibroblasts are associated with many different tumors. Myofibroblasts, activated fibroblasts, and perivascular mesenchymal cells such as pericytes play a role in cancer progression. Many studies suggest that myofibroblasts facilitate tumor growth and cancer progression. The source for myofibroblasts and other activated fibroblasts within the tumors is still debated. Although de novo activation of quiescent fibroblasts into alpha-smooth muscle actin (alpha SMA)-positive myofibroblasts is one likely source, epithelial to mesenchymal transition and bone marrow recruitment are also evolving as possible mechanisms for the emergence of a heterogeneous population of carcinoma-associated fibroblasts. Here, we show that transforming growth factor-beta1 could induce proliferating endothelial cells to undergo a phenotypic conversion into fibroblast-like cells. Such endothelial to mesenchymal transition (EndMT) is associated with the emergence of mesenchymal marker fibroblast-specific protein-1 (FSP1) and down-regulation of CD31/PECAM. Additionally, we show EndMT in tumors using the B16F10 melanoma model and the Rip-Tag2 spontaneous pancreatic carcinoma model. Crossing Tie2-Cre mice with R26Rosa-lox-Stop-lox-LacZ mice allows for irreversible tagging of endothelial cells. We provide unequivocal evidence for EndMT at the invasive front of the tumors in these transgenic mice. Collectively, our results show that EndMT is a unique mechanism for the accumulation of carcinoma-associated fibroblasts and suggest that antiangiogenic treatment of tumors may have a direct effect in decreasing activated fibroblasts that likely facilitate cancer progression.
Vector Competence of Glossina palpalis gambiensis for Trypanosoma brucei s.l. and Genetic Diversity of the Symbiont Sodalis glossinidius
Authors: A. Geiger, S. Ravel, T. Mateille, J. Janelle, D. Patrel, G. Cuny, R. Frutos
Journal: Molecular Biology and Evolution (2006)

Tsetse flies transmit African trypanosomes, responsible for sleeping sickness in humans and nagana in animals. This disease affects many people with considerable impact on public health and economy in sub-Saharan Africa, whereas trypanosomes' resistance to drugs is rising. The symbiont Sodalis glossinidius is considered to play a role in the ability of the fly to acquire trypanosomes. Different species of Glossina were shown to harbor genetically distinct populations of S. glossinidius. We therefore investigated whether vector competence for a given trypanosome species could be linked to the presence of specific genotypes of S. glossinidius. Glossina palpalis gambiensis individuals were fed on blood infected either with Trypanosoma brucei gambiense or Trypanosoma brucei brucei. The genetic diversity of S. glossinidius strains isolated from infected and noninfected dissected flies was investigated using amplified fragment length polymorphism markers. Correspondence between occurrence of these markers and parasite establishment was analyzed using multivariate analysis. Sodalis glossinidius strains isolated from T. brucei gambiense-infected flies clustered differently than that isolated from T. brucei brucei-infected individuals. The ability of T. brucei gambiense and T. brucei brucei to establish in G. palpalis gambiensis insect midgut is statistically linked to the presence of specific genotypes of S. glossinidius. This could explain variations in Glossina vector competence in the wild. Then, assessment of the prevalence of specific S. glossinidius genotypes could lead to novel risk management strategies.
CD4+ cytolytic T cell clone confers protection against murine malaria.
Authors: M Tsuji, P Romero, R S Nussenzweig, F Zavala
Journal: The Journal of Experimental Medicine (1990)

A CD4+ T cell clone (A1.6) was derived from spleen cells of mice immunized with irradiated sporozoites. This T cell clone recognizes an antigen that is shared by sporozoites and blood forms of Plasmodium berghei and differs from the circumsporozoite protein. Clone A1.6 displays cytotoxic activity, produces IFN-gamma and IL-2 in vitro, and recognizes the plasmodial antigen in the context of the class II I-Ed molecule. Passive transfer of this CD4+ clone into naive mice resulted in a high degree of protection against sporozoite challenge.
"Popcorn worker's lung" in Britain in a man making potato crisp flavouring
Authors: D J Hendrick
Journal: Thorax (2008)

The case history is presented of a patient who developed "popcorn worker's lung" following exposure to 2,3-butanedione (diacetyl). Other similar cases are reviewed, and it is concluded that "food flavourer's lung" may be a more suitable diagnostic label.
Arthritis and the Risk of Falling Into Poverty: A Survival Analysis Using Australian Data
Authors: Emily J. Callander, Deborah J. Schofield
Journal: Arthritis & Rheumatology (2015)

Low income is known to be associated with having arthritis. However, no longitudinal studies have documented the relationship between developing arthritis and falling into poverty. The purpose of this study was to evaluate Australians who developed arthritis to determine if they had an elevated risk of falling into poverty.Survival analysis using Cox regression models was applied to nationally representative, longitudinal survey data obtained between January 1, 2007 and December 31, 2012 from Australian adults who were ages 21 years and older in 2007.The hazard ratio for falling into income poverty was 1.08 (95% confidence interval [95% CI] 1.06-1.09) in women who were diagnosed as having arthritis and 1.15 (95% CI 1.13-1.16) in men who were diagnosed as having arthritis, as compared to those who were never diagnosed as having arthritis. The hazard ratio for falling into multidimensional poverty was 1.15 (95% CI 1.14-1.17) in women who were diagnosed as having arthritis and 1.88 (95% CI 1.85-1.91) in men who were diagnosed as having arthritis.Developing arthritis increases the risk of falling into income poverty and multidimensional poverty. The risk of multidimensional poverty is greater than the risk of income poverty. Given the high prevalence of arthritis, the condition is likely an overlooked driver of poverty.
A rare cryptic translation product is presented by Kb major histocompatibility complex class I molecule to alloreactive T cells.
Authors: S Malarkannan, M Afkarian, N Shastri
Journal: The Journal of Experimental Medicine (1995)

The identity of allogeneic peptide/major histocompatibility complex (MHC) complexes that elicit vigorous T cell responses has remained an interesting problem for both practical and theoretical reasons. Although a few abundant MHC class I-bound peptides have been purified and sequenced, identifying the unique T cell-stimulating peptides from among the thousands of existing peptides is still a very difficult undertaking. In this report, we identified the antigenic peptide that is recognized by an alloreactive bm1 anti-B6 T cell clone using a novel genetic strategy that is based upon measurement of T cell receptor occupancy in single T cells. Using lacZ-inducible T cells as a probe, we screened a splenic cDNA library in transiently transfected antigen-presenting cells (APCs) and isolated a cDNA clone that allowed expression of the appropriate peptide/Kb MHC complex in APC. The antigenic octapeptide (SVVEFSSL) exactly matched the consensus Kb MHC motif, but was surprisingly encoded by a non-ATG defined translation reading frame. Furthermore, the abundance of the naturally processed analog in untransfected cells was estimated to be &amp;lt;10 copies per cell. These results illustrate a novel strategy for identifying T cell-stimulating antigens in general and directly show that alloreactive T cells can respond to rather rare peptide/MHC complexes. These results also suggest that the total pool of processed peptides expressed on the APC surface may include those generated by cryptic translation of normally expressed transcripts.
Duration and breaks in sedentary behaviour: accelerometer data from 1566 community-dwelling older men (British Regional Heart Study)
Authors: Barbara J Jefferis, Claudio Sartini, Eric Shiroma, Peter H Whincup, S Goya Wannamethee, I-Min Lee
Journal: British Journal of Sports Medicine (2014)

Sedentary behaviours are increasingly recognised as raising the risk of cardiovascular disease events, diabetes and mortality, independently of physical activity levels. However, little is known about patterns of sedentary behaviour in older adults.Cross-sectional study of 1566/3137 (50% response) men aged 71-91 years from a UK population-based cohort study. Men wore a GT3x accelerometer over the hip for 1 week in 2010-2011. Mean daily minutes of sedentary behaviours, percentage of day in sedentary behaviours, sedentary bouts and breaks were calculated and summarised by health and demographic characteristics.1403 ambulatory men aged 78.4 years (SD=4.6 years) with ≥ 600 min of accelerometer wear on ≥ 3 days had complete data on covariables. Men spent on average 618 min (SD=83), or 72% of their day in sedentary behaviours (<100 counts/min). On average, men accumulated 72 spells of sedentary behaviours per day, with 7 breaks in each sedentary hour. Men had on average 5.1 sedentary bouts of ≥ 30 min, which accounted for 43% of sedentary time, and 1.4 bouts of ≥ 60 min, which accounted for 19% of daily sedentary time. Men who were over 80 years old, obese, depressed and had multiple chronic conditions accumulated more sedentary time and spent more time in longer sedentary bouts.Older men spend nearly three quarters of their day in sedentary behaviours, mostly accumulated in short bouts, although bouts lasting ≥ 30 min accounted for nearly half of the sedentary time each day. Men with medical risk factors were more likely to also display sedentary behaviour.
Invariant natural killer T cells recognize a fungal glycosphingolipid that can induce airway hyperreactivity
Authors: Lee A Albacker, Vinod Chaudhary, Ya-Jen Chang, Hye Young Kim, Ya-Ting Chuang, Muriel Pichavant, Rosemarie H DeKruyff, Paul B Savage, Dale T Umetsu
Journal: Nature Medicine (2013)
Neonatal outcomes among singleton births after blastocyst versus cleavage stage embryo transfer: a systematic review and meta-analysis
Authors: S. Dar, T. Lazer, P. S. Shah, C. L. Librach
Journal: Human Reproduction Update (2014)

BACKGROUNDSeveral studies have evaluated outcomes of singleton pregnancies after blastocyst versus cleavage stage embryo transfer. Higher incidences of preterm birth (PTB), very preterm birth (VPTB), low birthweight (LBW) and congenital malformations were identified in a few of them. The objective of our study was to systematically review and meta-analyze pregnancy and neonatal outcomes among singleton births following blastocyst versus cleavage stage embryo transfer.
PTEN-Mediated Resistance to Epidermal Growth Factor Receptor Kinase Inhibitors
Authors: Ingo K. Mellinghoff, Tim F. Cloughesy, Paul S. Mischel
Journal: Clinical Cancer Research (2007)

Abstract Molecularly targeted therapies are transforming the treatment of cancer. Elucidating the dynamic signaling networks that underlie sensitivity and resistance to these inhibitors is critical for successful clinical application. There is considerable evidence to suggest that constitutively activating mutations in kinases that regulate cellular growth may result in tumor cell “addiction” and favorable response to targeted inhibition. However, there is emerging evidence to suggest that clinical response may also be determined by other changes in the molecular circuitry of cancer cells, such as loss of key tumor-suppressor proteins. Here, we will discuss resistance to epidermal growth factor receptor tyrosine kinase inhibitors in glioblastoma patients that is mediated by loss of the PTEN tumor-suppressor protein.
The influence of pre-exercise glucose ingestion on endurance running capacity.
Authors: C Chryssanthopoulos, L C Hennessy, C Williams
Journal: British Journal of Sports Medicine (1994)

Drinking a concentrated glucose solution less than 1 h before the start of prolonged submaximal exercise has been reported to reduce endurance capacity during cycling. The purpose of this study was to re-examine the influence of pre-exercise ingestion of a concentrated glucose solution on endurance running capacity. Nine recreational runners (five men and four women) ran to exhaustion on a level treadmill, at speeds equivalent to 70% VO2max, on two occasions separated by at least 1 week. The runners ingested either a solution containing 75 g of glucose in 300 ml of water (G trial), or 300 ml of sweetened water (P trial) 30 min before each trial. As a consequence, the blood glucose concentrations were 55% higher at the beginning of the G trial compared with those recorded for the P trial (G trial, mean(s.e.) blood glucose = 6.3(0.7) mmol l-1 versus P trial, mean(s.e.) blood glucose = 4.1(0.3) mmol l-1; P &lt; 0.01). Nevertheless, there were no differences in the running times to exhaustion between the two trials (G trial, mean(s.e.) 133.79(11.0) min versus P trial, mean(s.e.) 121.16(8.1) min). The results of this study show that ingesting a 25% glucose solution 30 min before exercise does not reduce the endurance capacity of recreational runners when the exercise intensity is equivalent to 70% VO2max.
Addition of dimethylsulphoxide to methyl-tert-butyl ether and ethyl propionate increases cholesterol dissolving capacity and cholesterol gall stone dissolution in vitro.
Authors: J J Bergman, A K Groen, K Huibregtse, G N Tytgat
Journal: Gut (1994)

There is a discrepancy between in vitro cholesterol dissolving efficacy of methyl-tert-butyl ether (MTBE) and ethyl propionate and cholesterol gall stone dissolution in vivo. This study investigated whether the presence of bile changes the cholesterol dissolving capacity of MTBE and ethyl propionate. The addition of dimethylsulphoxide to MTBE or ethyl propionate was also studied to discover if it improves the dissolving capacity for cholesterol gall stones. The presence of bile caused a 25% decrease in cholesterol dissolving capacity of both MTBE and ethyl propionate (p &lt; 0.0001). This inhibitory effect of bile could be overcome by the addition of dimethyl-sulphoxide: dimethylsulphoxide caused an increase in cholesterol dissolving capacity of MTBE and ethyl propionate, the increase depending on the dimethyl-sulphoxide/bile ratio in the mixture. Mean dissolution time of weight, size, and patient matched cholesterol gall stones was 220 minutes in MTBE and 130 minutes in MTBE/dimethylsulphoxide (p &lt; 0.0001). No stones dissolved completely in ethyl propionate or ethyl propionate/dimethyl-sulphoxide within 300 minutes. In conclusion, MTBE/dimethylsulphoxide is a more potent dissolving agent for cholesterol gall stones than MTBE, giving a 40% reduction in dissolution time. Addition of dimethylsulphoxide to ethyl propionate does not result in faster stone dissolution. MTBE and MTBE/dimethylsulphoxide are far superior to ethyl propionate as solvents for cholesterol gall stones.
Risk and the Efficacy of Antiinflammatory Agents
Authors: Peter Q. Eichacker, Chantal Parent, Andre Kalil, Claire Esposito, Xizhong Cui, Steven M. Banks, Eric P. Gerstenberger, Yvonne Fitz, Robert L. Danner, Charles Natanson
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

We investigated whether a relationship between risk of death and treatment effect could explain the disparate results between the preclinical and clinical sepsis trials of antiinflammatory agents over the last decade. A metaregression analysis of cited preclinical studies showed that the treatment effects of these agents were highly dependent on risk of death (p = 0.0001) and that animals were studied at significantly higher control mortality rates than humans (median [25th-75th quartile], 88% [79-96%] versus 39% [32-42%], p = 0.0001). An analysis of the clinical trials showed that antiinflammatory agents were also significantly more efficacious in septic patients with higher risk of death (p = 0.002) and were harmful in those with low risk. To test this relationship prospectively, we studied antiinflammatory agents in models employing differing doses of bacterial challenge to produce the full range of risk of death. We found that the efficacy of these agents, although very beneficial at high control mortality rates, was much reduced (p = 0.0001) and similar to those in human trials at moderate control mortality rates (i.e., 30 to 40%). The efficacy of antiinflammatory agents during sepsis is dependent on the risk of death, an observation that explains the apparent contradiction between preclinical and clinical trial results. Accounting for this relationship may be necessary for the safe and effective development of antiinflammatory therapies for sepsis.
Safety and Efficacy of Romiplostim in Patients With Lower-Risk Myelodysplastic Syndrome and Thrombocytopenia
Authors: Hagop Kantarjian, Pierre Fenaux, Mikkael A. Sekeres, Pamela S. Becker, Adam Boruchov, David Bowen, Eva Hellstrom-Lindberg, Richard A. Larson, Roger M. Lyons, Petra Muus, Jamile Shammo, Robert Siegel, Kuolung Hu, Janet Franklin, Dietmar P. Berger
Journal: Journal of Clinical Oncology (2009)

To assess the safety and efficacy of romiplostim, a peptibody that increases platelet production, for treatment of thrombocytopenic patients with myelodysplastic syndromes (MDS).Eligible patients had lower-risk MDS (International Prognostic Scoring System low or intermediate 1), a mean baseline platelet count <or= 50 x 10(9)/L, and were only receiving supportive care. Patients received three injections of 300, 700, 1,000, or 1,500 microg romiplostim at weekly intervals. After evaluation of platelet response at week 4, patients could continue to receive romiplostim in a treatment extension phase for up to 1 year.All 44 patients who enrolled completed the treatment phase; 41 patients continued into the extension phase. Median platelet counts increased throughout the study, from fewer than 30 x 10(9)/L at baseline to 60, 73, 38, and 58 x 10(9)/L at week 4 for the 300-, 700-, 1,000-, and 1,500 -microg dose cohorts, respectively. A durable platelet response (per International Working Group 2000 criteria for 8 consecutive weeks independent of platelet transfusions) was achieved by 19 patients (46%). The incidence of bleeding events and platelet transfusions was less common among patients who achieved a durable platelet response than those who did not (4.3 v 39.3 per 100 patient-weeks). Forty-three patients (98%) reported one or more adverse events. Treatment-related serious adverse events were reported in five patients (11%), all of whom were in the 1,500-microg dose cohort. Two patients progressed to acute myeloid leukemia during the study. No neutralizing antibodies to either romiplostim or endogenous thrombopoietin were seen.Romiplostim appeared well-tolerated in this study and may be a useful treatment for patients with MDS and thrombocytopenia.