tbuckley/cabot-search huggingface dataset:
Annotation and analysis of 10,000 expressed sequence tags from developing mouse eye and adult retina.
Authors: Jindan Yu, Rafal Farjo, Sean P MacNee, Wolfgang Baehr, Dwight E Stambolian, Anand Swaroop
Journal: Genome biology (2003)

As a biomarker of cellular activities, the transcriptome of a specific tissue or cell type during development and disease is of great biomedical interest. We have generated and analyzed 10,000 expressed sequence tags (ESTs) from three mouse eye tissue cDNA libraries: embryonic day 15.5 (M15E) eye, postnatal day 2 (M2PN) eye and adult retina (MRA).Annotation of 8,633 non-mitochondrial and non-ribosomal high-quality ESTs revealed that 57% of the sequences represent known genes and 43% are unknown or novel ESTs, with M15E having the highest percentage of novel ESTs. Of these, 2,361 ESTs correspond to 747 unique genes and the remaining 6,272 are represented only once. Phototransduction genes are preferentially identified in MRA, whereas transcripts for cell structure and regulatory proteins are highly expressed in the developing eye. Map locations of human orthologs of known genes uncovered a high density of ocular genes on chromosome 17, and identified 277 genes in the critical regions of 37 retinal disease loci. In silico expression profiling identified 210 genes and/or ESTs over-expressed in the eye; of these, more than 26 are known to have vital retinal function. Comparisons between libraries provided a list of temporally regulated genes and/or ESTs. A few of these were validated by qRT-PCR analysis.Our studies present a large number of potentially interesting genes for biological investigation, and the annotated EST set provides a useful resource for microarray and functional genomic studies.
Contraceptives on the N.H.S
Authors: J. Cantor
Journal: BMJ (1973)

It was with some misgiving that I read in my morning paper that as from 1 April 1974 all contraceptives are to be made available on National Health Service prescription.  Some 7 months ago my partner and I found that the number of women in our practice on the pill was assuming such proportions that we were unable to be as thorough in our 6-monthly check-ups as we wished.  We therefore decided to employ on a sessional basis a woman doctor who devoted all her available time to family planning work.  The result has been most encouraging and the 75p for prescribing the pill has been a great help in her renumeration.  Can I take it that as from 1 April 1974 family planning will be yet another item the general practitioner must carry out with no extra renumeration?  If so I am sure a great many G.P.s will discontinue any form of regular examination for these women.  Even at the present time numerous women arriving in this area have been astonished to learn that they are unable to obtain a repeat prescription without an examination.  So far as condoms are concerned I did not study medicine with the ideas of supplying these articles.  If the general public are to have condoms on the N.H.S. I suggest that family planning clinics supply them or possibly the local health or welfare departments.  As a medical examination is not necessary before a condom is worn I do not propose to issue prescriptions for these articles and feel that many G.P.s will follow suit.(FULL TEXT)
Is pulmonary embolism a common cause of chronic pulmonary hypertension? Limitations of the embolic hypothesis
Authors: P. Egermayer, A.J. Peacock
Journal: European Respiratory Journal (2000)

The hypothesis that chronic thromboembolic pulmonary hypertension results from unresolved pulmonary embolism has strongly influenced the diagnosis and management of this disease since the 1960s. However, it is nearly impossible to induce chronic pulmonary hypertension in any animal species by means of repeated embolization of thrombotic material. The haemodynamic effects of thrombotic pulmonary embolism of different degrees of magnitude have also been studied in humans and there is little to suggest that chronic pulmonary hypertension is a likely long term outcome. Furthermore many conditions which predispose to venous thromboembolism do not appear to cause thromboembolic pulmonary hypertension. Other arteriopathic and atherosclerotic risk factors, are found in patients with chronic thromboembolic pulmonary hypertension, but not in those with venous thrombosis, suggesting that these may be unrelated conditions. Thrombosis in situ of the pulmonary arteries is common in severe pulmonary hypertension of any cause. Such thrombosis cannot usually be distinguished from pulmonary embolism. It is hypothesized that in situ thrombosis and pulmonary arteriopathy are common causes of vascular occlusion which is usually diagnosed as "chronic thromboembolic pulmonary hypertension" and that venous thromboembolism is unlikely to be a common cause of chronic pulmonary hypertension. It is further hypothesized that pulmonary embolism is seldom the sole cause of "chronic thromboembolic pulmonary hypertension".
Adjuvant Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer After D2 Gastrectomy: Final Results From the Classic Trial
Authors: Sung Hoon Noh, Sook Ryun Park, Han-Kwang Yang, Hyun Cheol Chung, Ik-Joo Chung, Kyung Hee Lee, Hyung-Ho Kim, Jiafu Ji, Jen-Shi Chen, Yunni Lim, Stella Ha, Yung-Jue Bang
Journal: Annals of Oncology (2013)
The Stepwise Evolution of Early Life Driven by Energy Conservation
Authors: J. G. Ferry
Journal: Molecular Biology and Evolution (2006)

Two main theories have emerged for the origin and early evolution of life based on heterotrophic versus chemoautotrophic metabolisms. With the exception of a role for CO, the theories have little common ground. Here we propose an alternative theory for the early evolution of the cell which combines principal features of the widely disparate theories. The theory is based on the extant pathway for conversion of CO to methane and acetate, largely deduced from the genomic analysis of the archaeon Methanosarcina acetivorans. In contrast to current paradigms, we propose that an energy-conservation pathway was the major force which powered and directed the early evolution of the cell. We envision the proposed primitive energy-conservation pathway to have developed sometime after a period of chemical evolution but prior to the establishment of diverse protein-based anaerobic metabolisms. We further propose that energy conservation played the predominant role in the later evolution of anaerobic metabolisms which explains the origin and evolution of extant methanogenic pathways.
Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG)
Authors: Winfred C Wang, Russell E Ware, Scott T Miller, Rathi V Iyer, James F Casella, Caterina P Minniti, Sohail Rana, Courtney D Thornburg, Zora R Rogers, Ram V Kalpatthi, Julio C Barredo, R Clark Brown, Sharada A Sarnaik, Thomas H Howard, Lynn W Wynn, Abdullah Kutlar, F Daniel Armstrong, Beatrice A Files, Jonathan C Goldsmith, Myron A Waclawiw, Xiangke Huang, Bruce W Thompson
Journal: The Lancet (2011)
GPs should get specific training on dealing with patients' alcohol problems, MPs hear
Authors: A. O'Dowd
Journal: BMJ (2009)

With the right training and support, doctors could take on the role of preventing the overuse of alcohol by their patients as part of routine care, MPs were told earlier this month.

At an evidence session as part of the parliamentary health select committee’s inquiry into alcohol, expert witnesses said that primary care could do more to help patients with alcohol problems.

MPs asked clinicians what more the NHS could do to prevent the development of alcohol related problems.

Mike Kelly, director of the Centre for Public Health Excellence at the National Institute for Health and Clinical Excellence, said that the institute was currently undertaking three related reviews: prevention of …
Hedgehog Signaling and Bmi-1 Regulate Self-renewal of Normal and Malignant Human Mammary Stem Cells
Authors: Suling Liu, Gabriela Dontu, Ilia D. Mantle, Shivani Patel, Nam-shik Ahn, Kyle W. Jackson, Prerna Suri, Max S. Wicha
Journal: Cancer Research (2006)

Abstract The epithelial components of the mammary gland are thought to arise from stem cells with a capacity for self-renewal and multilineage differentiation. Furthermore, these cells and/or their immediate progeny may be targets for transformation. We have used both in vitro cultivation and a xenograft mouse model to examine the role of hedgehog signaling and Bmi-1 in regulating self-renewal of normal and malignant human mammary stem cells. We show that hedgehog signaling components PTCH1, Gli1, and Gli2 are highly expressed in normal human mammary stem/progenitor cells cultured as mammospheres and that these genes are down-regulated when cells are induced to differentiate. Activation of hedgehog signaling increases mammosphere-initiating cell number and mammosphere size, whereas inhibition of the pathway results in a reduction of these effects. These effects are mediated by the polycomb gene Bmi-1. Overexpression of Gli2 in mammosphere-initiating cells results in the production of ductal hyperplasia, and modulation of Bmi-1 expression in mammosphere-initiating cells alters mammary development in a humanized nonobese diabetic-severe combined immunodeficient mouse model. Furthermore, we show that the hedgehog signaling pathway is activated in human breast “cancer stem cells” characterized as CD44+CD24−/lowLin−. These studies support a cancer stem cell model in which the hedgehog pathway and Bmi-1 play important roles in regulating self-renewal of normal and tumorigenic human mammary stem cells. (Cancer Res 2006; 66(12): 6063-71)
THE PERFORMANCE OF BASELINE HAEMODYNAMIC INDICES OF CORONARY DISEASE SEVERITY IN THE DEFER AND FAME STUDIES: AN ESTIMATED AGREEMENT OF STENOSES CLASSIFICATION WITH FRACTIONAL FLOW RESERVE
Authors: Ricardo Petraco da Cunha, Tim van de Hoef, Sukhjinder Nijjer, Sayan Sen, Javier Escaned, Martijn Meuwissen, Darrel Francis, Jan Piek, Justin Davies
Journal: Journal of the American College of Cardiology (2013)
Metabolically Healthy Obesity and Risk of Mortality
Authors: Guy-Marino Hinnouho, Sébastien Czernichow, Aline Dugravot, G. David Batty, Mika Kivimaki, Archana Singh-Manoux
Journal: Diabetes Care (2013)

To assess the association of a "metabolically healthy obese" phenotype with mortality using five definitions of metabolic health.Adults (n = 5,269; 71.7% men) aged 39-62 years in 1991 through 1993 provided data on BMI and metabolic health, defined using data from the Adult Treatment Panel-III (ATP-III); criteria from two studies; and the Matsuda and homeostasis model assessment (HOMA) indices. Cross-classification of BMI categories and metabolic status (healthy/unhealthy) created six groups. Cox proportional hazards regression models were used to analyze associations with all-cause and cardiovascular disease (CVD) mortality during a median follow-up of 17.7 years.A total of 638 individuals (12.1% of the cohort) were obese, of whom 9-41% were metabolically healthy, depending on the definition. Regardless of the definition, compared with metabolically healthy, normal-weight individuals, both the metabolically healthy obese (hazard ratios [HRs] ranged from 1.81 [95% CI 1.16-2.84] for ATP-III to 2.30 [1.13-4.70] for the Matsuda index) and the metabolically abnormal obese (HRs ranged from 1.57 [1.08-2.28] for the Matsuda index to 2.05 [1.44-2.92] for criteria defined in a separate study) had an increased risk of mortality. The only exception was the lack of excess risk using the HOMA criterion for the metabolically healthy obese (1.08; 0.67-1.74). Among the obese, the risk of mortality did not vary as a function of metabolic health apart from when using the HOMA criterion (1.93; 1.15-3.22). Similar results were obtained for cardiovascular mortality.For most definitions of metabolic health, both metabolically healthy and unhealthy obese patients carry an elevated risk of mortality.
Maximum rate of tension fall during isometric relaxation at end-systolic fiber length in canine papillary muscle.
Authors: K Tamiya, S Kikkawa, A Gunji, M Hori, Y Sakurai
Journal: Circulation Research (1977)

We measured the characteristics of the decline in tension during isometric relaxation of canine papillary muscle. In the intact heart, relaxation begins with the isovolumic phase, but in experiments on papillary muscle previously reported the isotonic phase preceded the isometric phase during the course of relaxation. In our experiments, however, the isotonic bar was locked at the instant the muscle reached the end-systolic fiber length in order to hold the fiber at the length during the succeeding relaxation process. Therefore, we obtained a relaxation process similar to that occurring in the intact heart. The major results of these experiments are: (1) Maximum rate of the decline in tension (-dT/dtmax) is linearly related to the magnitude of total load. (2) -dT/dtmax is augmented by positive inotropic interventions and diminished by negative inotropic interventions. (3) An increase in preload results in only a slight increase in -dT/dtmax. (4) End-systolic fiber length itself is not a principal determinant of -dT/dtmax. (5) -dT/dtmax divided by total load is independent of the amount of muscle shortening. We, therefore, suggest that -dT/dtmax divided by total load cand be a useful index of the relaxation characteristics of cardiac muscle.
Tumor necrosis factor production during human renal allograft rejection is associated with depression of plasma protein C and free protein S levels and decreased intragraft thrombomodulin expression.
Authors: A Tsuchida, H Salem, N Thomson, W W Hancock
Journal: The Journal of Experimental Medicine (1992)

Fibrin deposition is a common accompaniment of renal allograft rejection, indicating disruption of the normal physiologic balance between procoagulant and anticoagulant pathways. In vitro, tumor necrosis factor (TNF) induces endothelial expression of the procoagulant, tissue factor, and downregulation of thrombomodulin, a key component of the thrombomodulin/protein C (PC)/protein S (PS) pathway, which normally maintains an anticoagulant state by inactivating thrombin, preventing further thrombin formation by degrading factors Va and VIIIa, and decreasing plasminogen activator inhibitor activity. Raised levels of TNF were recently demonstrated within the blood of patients during episodes of renal allograft injection, and may be an early and discriminatory marker of rejection. This led us to investigate prospectively whether monitoring of serum TNF levels was of value clinically, and was associated with effects on circulating PC and PS levels, or alterations in intragraft thrombomodulin expression. Plasma samples (n = 454) were collected three times/week from all patients (n = 25) undergoing renal transplantation during a 9-month consecutive period, and assayed by ELISA and functional assays for TNF, PC, and free PS (FPS). Portions of renal biopsies, taken to evaluate episodes of acute deterioration of renal function, were evaluated by immunoperoxidase labeling for the presence and distribution of TNF, thrombomodulin, PC, PS, thrombin, fibrin, and factors V and VIII. Comparison of 78 plasma samples collected during 26 episodes of biopsy-proven acute cellular rejection with samples collected during periods of stable renal function (n = 349) showed that TNF levels rose significantly (390 +/- 242 pg/ml, p less than 0.01) above background levels 3 days before rising serum creatinine concentrations, and peaked (2,426 +/- 978 pg/ml) on the day of clinical rejection. PC-antigen (Ag) concentrations also decreased 3 days before rejection (68 +/- 13%, p less than 0.05), and were maximally depressed (49% +/- 16%, p less than 0.001) on the day of rejection. FPS levels were normal until the day before rejection (63% +/- 8%, p less than 0.01) and, like PC, were maximally depressed (43 +/- 10%) at rejection. Plasma TNF levels were significantly and inversely correlated with PC-Ag (p less than 0.001) and FPS (p less than 0.005) levels during rejection, regardless of whether such rejection episodes were steroid responsive or required OKT3 monoclonal antibody therapy. TNF, PC, and FPS levels were normal during episodes of cyclosporine toxicity and viral infection.(ABSTRACT TRUNCATED AT 400 WORDS)
A Phase I Study of Sunitinib plus Bevacizumab in Advanced Solid Tumors
Authors: Brian I. Rini, Jorge A. Garcia, Matthew M. Cooney, Paul Elson, Allison Tyler, Kristi Beatty, Joseph Bokar, Tarek Mekhail, R.M. Bukowski, G. Thomas Budd, Pierre Triozzi, Ernest Borden, Percy Ivy, Helen X. Chen, Afshin Dowlati, Robert Dreicer
Journal: Clinical Cancer Research (2009)

Bevacizumab is an antibody against vascular endothelial growth factor; sunitinib is an inhibitor of vascular endothelial growth factor and related receptors. The safety and maximum tolerated dose of sunitinib plus bevacizumab was assessed in this phase I trial.Patients with advanced solid tumors were treated on a 3+3 trial design. Patients received sunitinib daily (starting dose level, 25 mg) for 4 weeks on followed by 2 weeks off and bevacizumab (starting dose level, 5 mg/kg) on days 1, 15, and 29 of a 42-day cycle. Dose-limiting toxicities during the first 6-week cycle were used to determine the maximum tolerated dose.Thirty-eight patients were enrolled. Patients received a median of 3 cycles of treatment (range, 1-17(+)). There was one dose-limiting toxicity (grade 4 hypertension) at 37.5 mg sunitinib and 5 mg/kg bevacizumab. Grade 3 or greater toxicity was observed in 87% of patients including hypertension (47%), fatigue (24%), thrombocytopenia (18%), proteinuria (13%), and hand-foot syndrome (13%). Dose modifications and delays were common at higher dose levels. No clinical or laboratory evidence of microangiopathic hemolytic anemia was observed. Seven patients had a confirmed Response Evaluation Criteria in Solid Tumors-defined partial response (18%; 95% confidence interval, 8-34%). Nineteen of the 32 patients with a postbaseline scan (59%) had at least some reduction in overall tumor burden (median, 32%; range, 3-73%).The combination of sunitinib and bevacizumab in patients with advanced solid tumors is feasible, albeit with toxicity at higher dose levels and requiring dose modification with continued therapy. Antitumor activity was observed across multiple solid tumors.
The transcriptional landscape of Chlamydia pneumoniae
Authors: Marco Albrecht, Cynthia M Sharma, Marcus T Dittrich, Tobias Müller, Richard Reinhardt, Jörg Vogel, Thomas Rudel
Journal: Genome biology (2011)

Gene function analysis of the obligate intracellular bacterium Chlamydia pneumoniae is hampered by the facts that this organism is inaccessible to genetic manipulations and not cultivable outside the host. The genomes of several strains have been sequenced; however, very little information is available on the gene structure and transcriptome of C. pneumoniae. Using a differential RNA-sequencing approach with specific enrichment of primary transcripts, we defined the transcriptome of purified elementary bodies and reticulate bodies of C. pneumoniae strain CWL-029; 565 transcriptional start sites of annotated genes and novel transcripts were mapped. Analysis of adjacent genes for co-transcription revealed 246 polycistronic transcripts. In total, a distinct transcription start site or an affiliation to an operon could be assigned to 862 out of 1,074 annotated protein coding genes. Semi-quantitative analysis of mapped cDNA reads revealed significant differences for 288 genes in the RNA levels of genes isolated from elementary bodies and reticulate bodies. We have identified and in part confirmed 75 novel putative non-coding RNAs. The detailed map of transcription start sites at single nucleotide resolution allowed for the first time a comprehensive and saturating analysis of promoter consensus sequences in Chlamydia. The precise transcriptional landscape as a complement to the genome sequence will provide new insights into the organization, control and function of genes. Novel non-coding RNAs and identified common promoter motifs will help to understand gene regulation of this important human pathogen.
Defining the Ideal Injection Techniques When Using 5-mm Needles in Children and Adults
Authors: Paul Leslie Hofman, José Guilherme Behrensdorf Derraik, Teresa Elizabeth Pinto, Sheryl Tregurtha, Ann Faherty, Jane Michele Peart, Paul Leslie Drury, Elizabeth Robinson, Ramin Tehranchi, Morten Donsmark, Wayne Stephen Cutfield
Journal: Diabetes Care (2010)

OBJECTIVE We aimed to establish the ideal injection techniques using 5-mm needles to reliably inject insulin into the subcutaneous fat in both children and adults and to quantify the associated pain and leakage of the test medium. RESEARCH DESIGN AND METHODS A total of 259 subjects (122 children/adolescents and 137 adults) were injected with sterile air corresponding to 20 IU insulin (200 μl) with 32-G 5-mm needles at 90° or 45°, in the abdomen and thigh, and with or without a pinched skin fold. Injection depth was assessed via ultrasonography. Subjects rated pain on a visual analog scale. Test medium injections into the abdomen and thigh (0.2–0.6 ml) were also administered to assess injection leakage. RESULTS Among children, 5.5% of injections were intramuscular (IM) and 0.5% were intradermal, while in adults, the incidence was 1.3 and 0.6%, respectively. The frequency of IM injections was greater in boys and negligible among adult women. Subcutaneous fat thickness was the primary predictor of the likelihood of IM injections (P &amp;lt; 0.001). A third of all patients reported experiencing no pain during insulin injection, with children/adolescents experiencing considerably more discomfort than adults. Some leakage of medium was observed, but was unrelated to injection volume and was generally minimal. CONCLUSIONS 5-mm needles are reliably inserted into subcutaneous fat in both adults and children. These needles were associated with reduced pain and minimal leakage. We recommend an angled injection with a pinched skin fold for children, while in adults, the technique should be left to patient preference.