tbuckley/cabot-search huggingface dataset:
Isolated hypocapnia: A sign not to be neglected
Authors: Aymen Ayari, Nawel Chaouch, Sawssen Bacha, Nouha Kortas, Hajer Racil, Sana Cheikh Rouhou, Abdellatif Chabbou
Journal: European Respiratory Journal (2014)

In pulmonary embolism (PE) hypocapnia is frequent and due to hyperventilation in response to hypoxemia. But unspecific clinical presentation with isolated hypocapnia and without hypoxemia were described.  To study clinical feature of PE with a normal arterial oxygen pressure (PaO2) but hypocapnia, we analyzed all cases of PE hospitalized in our department from January 2009 until December 2012. Only patients presenting PE and hypocapnia without hypoxemia were included. All PE cases were confirmed by CT angiography.  On 80 cases of PE only 15 patients met criteria (18.75%). All patients were men and 12 were smokers. Median age was 56.13 years. All cases had no suspected high risk PE. It was discovered incidentally in 8 cases. In the other cases the most frequent clinical signs were dyspnea, tachypnea and chest pain. Mean Pa O2 was 83mmHg and mean Pa CO2 was 27.4mmHg (26-34). PE was bilateral in 6 cases. Mean vascular obstruction index was 13.5% (5-22). PE was associated to lung cancer in 7 cases, COPD in 2 cases and IPF in 1 case. No underlying lung disease was found in 5 cases. PE Outcome was favorable in all cases.  PE with hypocapnia without hypoxemia is not scarce. It occurs often in relatively low high risk forms. Isolated hypocapnia should lead to evoke PE especially in patients with chronic lung disease.
Outcomes of patients with metastatic renal cell carcinoma that do not meet eligibility criteria for clinical trials
Authors: D.Y.C. Heng, T.K. Choueiri, B.I. Rini, J. Lee, T. Yuasa, S.K. Pal, S. Srinivas, G.A. Bjarnason, J.J. Knox, M. MacKenzie, U.N. Vaishampayan, M.H. Tan, S.Y. Rha, F. Donskov, N. Agarwal, C. Kollmannsberger, S. North, L.A. Wood
Journal: Annals of Oncology (2013)
Reticulate Representation of Evolutionary and Functional Relationships between Phage Genomes
Authors: G. Lima-Mendez, J. Van Helden, A. Toussaint, R. Leplae
Journal: Molecular Biology and Evolution (2008)

Bacteriophage genomes show pervasive mosaicism, indicating the importance of horizontal gene exchange in their evolution. Phage genomes represent unique combinations of modules, each of them with a different phylogenetic history. The traditional classification, based on a variety of criteria such as nucleic acid type (single/double-stranded DNA/RNA), morphology, and host range, appeared inconsistent with sequence analyses. With the genomic era, an ever increasing number of sequenced phages cannot be classified, in part due to a lack of morphological information and in part to the intrinsic incapability of tree-based methods to efficiently deal with mosaicism. This problem led some virologists to call for a moratorium on the creation of additional taxa in the order Caudovirales, in order to let virologists discuss classification schemes that might better suit phage evolution. In this context, we propose a framework for a reticulate classification of phages based on gene content. Starting from gene families, we built a weighted graph, where nodes represent phages and edges represent phage-phage similarities in terms of shared genes. We then apply various measures of graph topology to analyze the resulting graph. Most double-stranded DNA phages are found in a single component. The values of the clustering coefficient and closeness distinguish temperate from virulent phages, whereas chimeric phages are characterized by a high betweenness coefficient. We apply a 2-step clustering method to this graph to generate a reticulate classification of phages: Each phage is associated with a membership vector, which quantitatively characterizes its membership to the set of clusters. Furthermore, we cluster genes based on their "phylogenetic profiles" to define "evolutionary cohesive modules." In virulent phages, evolutionary modules span several functional categories, whereas in temperate phages they correspond better to functional modules. Moreover, despite the fact that modules only cover a fraction of all phage genes, phage groups can be distinguished by their different combination of modules, serving the bases for a higher level reticulate classification. These 2 classification schemes provide an automatic and dynamic way of representing the relationships within the phage population and can be extended to include newly sequenced phage genomes, as well as other types of genetic elements.
CCR5 Binds Multiple CC-Chemokines: MCP-3 Acts as a Natural Antagonist
Authors: Cédric Blanpain, Isabelle Migeotte, Benhur Lee, Jalal Vakili, Benjamin J. Doranz, Cédric Govaerts, Gilbert Vassart, Robert W. Doms, Marc Parmentier
Journal: Blood (1999)
Oncometabolite 2-Hydroxyglutarate Is a Competitive Inhibitor of α-Ketoglutarate-Dependent Dioxygenases
Authors: Wei Xu, Hui Yang, Ying Liu, Ying Yang, Ping Wang, Se-Hee Kim, Shinsuke Ito, Chen Yang, Pu Wang, Meng-Tao Xiao, Li-xia Liu, Wen-qing Jiang, Jing Liu, Jin-ye Zhang, Bin Wang, Stephen Frye, Yi Zhang, Yan-hui Xu, Qun-ying Lei, Kun-Liang Guan, Shi-min Zhao, Yue Xiong
Journal: Cancer Cell (2011)
5,6-epoxyeicosatrienoic acid, a novel arachidonate metabolite. Mechanism of vasoactivity in the rat.
Authors: M A Carroll, M P Garcia, J R Falck, J C McGiff
Journal: Circulation Research (1990)

We have reported that 5,6-epoxyeicosatrienoic acid (5,6-EET) was the only cytochrome P-450-dependent arachidonic acid (AA) epoxide to dilate the isolated, perfused caudal artery of the rat. We have investigated the mechanisms by which 5,6-EET dilates the rat-tail artery by studying the effect of deendothelialization and inhibition of AA metabolic pathways (cyclooxygenase, lipoxygenase, and cytochrome P-450 monooxygenase) on the vascular action of the epoxide. Rat isolated caudal arteries were perfused with Krebs-Henseleit solution at 37 degrees C, pH 7.4, and gassed with 95% O2-5% CO2. Arterial tone was elevated with phenylephrine; acetylcholine (0.5 nmol) was used to detect the presence of intact, functional endothelium. Doses of 5,6-EET, from 6.25 to 25.0 nmol, were injected close-arterially. After obtaining control responses, the same doses were randomly retested after deendothelialization or in the presence of inhibitors of AA metabolism. Removal of the endothelium decreased by 70% the vasodilator responses to 5,6-EET. The endothelial dependency was a function of the epoxide interacting with cyclooxygenase of the endothelium, because indomethacin (3 microM) and aspirin (50 microM) prevented the vasodilator response to 5,6-EET while not affecting the response to acetylcholine. SKF-525A (1.1 microM) and metyrapone (150 microM) did not affect the responses to the 5,6-EET, whereas clotrimazole (0.7 microM) and nordihydroguaiaretic acid (2.5 microM) had nonspecific effects, decreasing responses to 5,6-EET and acetylcholine. Because 5,6-EET failed to stimulate detectable release of prostanoids into the effluent from the caudal artery, we conclude that 5,6-EET requires conversion by cyclooxygenase for expression of its vasoactivity.
Factors Associated With 5-Year Risk of Hip Fracture in Postmenopausal Women
Authors: John Robbins, Aaron K. Aragaki, Charles Kooperberg, Nelson Watts, Jean Wactawski-Wende, Rebecca D. Jackson, Meryl S. LeBoff, Cora E. Lewis, Zhao Chen, Marcia L. Stefanick, Jane Cauley
Journal: JAMA (2007)

The 329,000 hip fractures that annually occur in the United States are associated with high morbidity, mortality, and cost. Identification of those at high risk is a step toward prevention.To develop an algorithm to predict the 5-year risk of hip fracture in postmenopausal women.A total of 93,676 women who participated in the observational component of the Women's Health Initiative (WHI), a multiethnic longitudinal study, were used to develop a predictive algorithm based on commonly available clinical features. Selected factors that predicted hip fracture were then validated by 68,132 women who participated in the clinical trial. The model was tested in a subset of 10,750 women who had undergone dual-energy x-ray absorptiometry (DXA) scans for bone mass density assessment.The prediction of centrally adjudicated hip fracture, measured by the area under the receiver operator characteristic (ROC) curves.During a mean (SD) follow-up of 7.6 (1.7) years, 1132 hip fractures were identified among women participating in the observational study (annualized rate, 0.16%), whereas during a mean follow-up of 8.0 (1.7) years, 791 hip fractures occurred among women participating in the clinical trial (annualized rate, 0.14%). Eleven factors predicted hip fracture within 5 years: age, self-reported health, weight, height, race/ethnicity, self-reported physical activity, history of fracture after age 54 years, parental hip fracture, current smoking, current corticosteroid use, and treated diabetes. Receiver operating characteristic curves showed that the algorithm had an area under the curve of 80% (95% confidence interval [CI], 0.77%-0.82%) when tested in the cohort of different women who were in the clinical trial. A simplified point score was developed for the probability of hip fracture. Receiver operating characteristic curves comparing DXA-scan prediction based on a 10% subset of the cohort and the algorithm among those who participated the clinical trial were similar, with an area under the curve of 79% (95% CI, 73%-85%) vs 71% (95% CI, 66%-76%).This algorithm, based on 11 clinical factors, may be useful to predict the 5-year risk of hip fracture among postmenopausal women of various ethnic backgrounds. Further studies are needed to assess the clinical implication of the algorithm in general and specifically to identify treatment benefits.
The effect of diversion of intestinal contents on the progress of Crohn's disease of the large bowel.
Authors: J H Burman, J A Williams, H Thompson, W T Cooke
Journal: Gut (1969)

This study shows that faecal diversion by ileostomy or colostomy results in an improvement in the patient's general health which is substantiated by the haematological and biochemical findings. However, in the bowel distal to the diversion there is always histological evidence of mucosal and transmural disease and complications such as fistulae may still occur. In only two patients (7%) was restoration of bowel continuity successful.
B cell priming for extrafollicular antibody responses requires Bcl-6 expression by T cells
Authors: Sau K. Lee, Robert J. Rigby, Dimitra Zotos, Louis M. Tsai, Shimpei Kawamoto, Jennifer L. Marshall, Roybel R. Ramiscal, Tyani D. Chan, Dominique Gatto, Robert Brink, Di Yu, Sidonia Fagarasan, David M. Tarlinton, Adam F. Cunningham, Carola G. Vinuesa
Journal: The Journal of Experimental Medicine (2011)

T follicular helper cells (Tfh cells) localize to follicles where they provide growth and selection signals to mutated germinal center (GC) B cells, thus promoting their differentiation into high affinity long-lived plasma cells and memory B cells. T-dependent B cell differentiation also occurs extrafollicularly, giving rise to unmutated plasma cells that are important for early protection against microbial infections. Bcl-6 expression in T cells has been shown to be essential for the formation of Tfh cells and GC B cells, but little is known about its requirement in physiological extrafollicular antibody responses. We use several mouse models in which extrafollicular plasma cells can be unequivocally distinguished from those of GC origin, combined with antigen-specific T and B cells, to show that the absence of T cell–expressed Bcl-6 significantly reduces T-dependent extrafollicular antibody responses. Bcl-6+ T cells appear at the T–B border soon after T cell priming and before GC formation, and these cells express low amounts of PD-1. Their appearance precedes that of Bcl-6+ PD-1hi T cells, which are found within the GC. IL-21 acts early to promote both follicular and extrafollicular antibody responses. In conclusion, Bcl-6+ T cells are necessary at B cell priming to form extrafollicular antibody responses, and these pre-GC Tfh cells can be distinguished phenotypically from GC Tfh cells.
Short-term walnut consumption increases circulating total adiponectin and apolipoprotein A concentrations, but does not affect markers of inflammation or vascular injury in obese humans with the metabolic syndrome: data from a double-blinded, randomized, placebo-controlled study
Authors: Konstantinos N. Aronis, Maria T. Vamvini, John P. Chamberland, Laura L. Sweeney, Aoife M. Brennan, Faidon Magkos, Christos S. Mantzoros
Journal: Metabolism (2011)
Capsid antigen presentation flags human hepatocytes for destruction after transduction by adeno-associated viral vectors
Authors: Gary C. Pien, Etiena Basner-Tschakarjan, Daniel J. Hui, Ashley N. Mentlik, Jonathan D. Finn, Nicole C. Hasbrouck, Shangzhen Zhou, Samuel L. Murphy, Marcela V. Maus, Federico Mingozzi, Jordan S. Orange, Katherine A. High
Journal: Journal of Clinical Investigation (2009)

Adeno-associated virus (AAV) vectors are effective gene delivery vehicles mediating long-lasting transgene expression. Data from a clinical trial of AAV2-mediated hepatic transfer of the Factor IX gene (F9) into hemophilia B subjects suggests that CTL responses against AAV capsid can eliminate transduced hepatocytes and prevent long-term F9 expression. However, the capacity of hepatocytes to present AAV capsid-derived antigens has not been formally demonstrated, nor whether transduction by AAV sensitizes hepatocytes for CTL-mediated destruction. To investigate the fate of capsids after transduction, we engineered a soluble TCR for the detection of capsid-derived peptide:MHC I (pMHC) complexes. TCR multimers exhibited antigen and HLA specificity and possessed high binding affinity for cognate pMHC complexes. With this reagent, capsid pMHC complexes were detectable by confocal microscopy following AAV-mediated transduction of human hepatocytes. Although antigen presentation was modest, it was sufficient to flag transduced cells for CTL-mediated lysis in an in vitro killing assay. Destruction of hepatocytes was inhibited by soluble TCR, demonstrating a possible application for this reagent in blocking undesirable CTL responses. Together, these studies provide a mechanism for the loss of transgene expression and transient elevations in aminotransferases following AAV-mediated hepatic gene transfer in humans and a potential therapeutic intervention to abrogate these limitations imposed by the host T cell response.
Human Mesenchymal Stem Cells as a Gene Delivery System to Create Cardiac Pacemakers
Authors: Irina Potapova, Alexei Plotnikov, Zhongju Lu, Peter Danilo, Virginijus Valiunas, Jihong Qu, Sergey Doronin, Joan Zuckerman, Iryna N. Shlapakova, Junyuan Gao, Zongming Pan, Alan J. Herron, Richard B. Robinson, Peter R. Brink, Michael R. Rosen, Ira S. Cohen
Journal: Circulation Research (2004)

We tested the ability of human mesenchymal stem cells (hMSCs) to deliver a biological pacemaker to the heart. hMSCs transfected with a cardiac pacemaker gene, mHCN2, by electroporation expressed high levels of Cs + -sensitive current (31.1±3.8 pA/pF at −150 mV) activating in the diastolic potential range with reversal potential of −37.5±1.0 mV, confirming the expressed current as I f -like. The expressed current responded to isoproterenol with an 11-mV positive shift in activation. Acetylcholine had no direct effect, but in the presence of isoproterenol, shifted activation 15 mV negative. Transfected hMSCs influenced beating rate in vitro when plated onto a localized region of a coverslip and overlaid with neonatal rat ventricular myocytes. The coculture beating rate was 93±16 bpm when hMSCs were transfected with control plasmid (expressing only EGFP) and 161±4 bpm when hMSCs were expressing both EGFP+mHCN2 ( P &lt;0.05). We next injected 10 6 hMSCs transfected with either control plasmid or mHCN2 gene construct subepicardially in the canine left ventricular wall in situ. During sinus arrest, all control (EGFP) hearts had spontaneous rhythms (45±1 bpm, 2 of right-sided origin and 2 of left). In the EGFP+mHCN2 group, 5 of 6 animals developed spontaneous rhythms of left-sided origin (rate=61±5 bpm; P &lt;0.05). Moreover, immunostaining of the injected regions demonstrated the presence of hMSCs forming gap junctions with adjacent myocytes. These findings demonstrate that genetically modified hMSCs can express functional HCN2 channels in vitro and in vivo, mimicking overexpression of HCN2 genes in cardiac myocytes, and represent a novel delivery system for pacemaker genes into the heart or other electrical syncytia.
Benefit-risk analysis of adalimumab versus methotrexate and placebo in the treatment of moderate to severe psoriasis: Comparison of adverse event–free response days in the CHAMPION trial
Authors: Kristian Reich, James Signorovitch, Karthik Ramakrishnan, Andrew P. Yu, Eric Q. Wu, Shiraz R. Gupta, Yanjun Bao, Parvez M. Mulani
Journal: Journal of the American Academy of Dermatology (2010)
The effects of selected submaximal short duration activities on S-T segment changes in active young men
Authors: Seyed Mostafa Tayebi, Fatah Moradi, Hassan Abdi
Journal: British Journal of Sports Medicine (2010)

Because of the physiologically significant electrical changes of heart following the short- or long-term physical activities, and diagnostic value of these changes, after or during the exercise training, researchers suggest that type, duration and intensity of physical activity play key roles in studying the ECG responses to exercise. The aim of the study was to investigate the effect of selected submaximal tests for estimating of VO 2 max (because of frequently use of them), as submaximal short duration activities, on ST segment changes in active young men. For this purpose, 13 healthy men were randomly selected from the physical education students at Urmia University. They had at least 3 years' experience in regular physical activity and sport participation. Measurements were made during four consecutive days (every day, 08:00). At 1st day, age (24.7±2.3 years), height (176.5±2.6 cm), weight (69.4±3.7 kg), and pretest ECGs were recorded. Subjects performed PWC 195 test, Katch-McArdle step test and Astrand ergometer test at 2nd, 3rd and 4th days, randomly. Immediately after the tests, post-test ECGs were recorded. Data were analysed using paired-sample t test (for comparison between pretest and each of post-tests) and one-way analysis of variance (for comparison among post-tests). Statistical significance was accepted at p&lt;0.001 and p&lt;0.05. Analysis of data indicated that all of three tests had significant effects on ST segment voltage (p&lt;0.001). Also, there were no significant differences between mean ST segment voltages of post-tests (p&lt;0.05) (rest: 0.053±0.017, PWC 195 test 0.023±0.011, Katch-McArdle step test 0.021±0.010, Astrand ergometer test 0.021±0.004 mv(. Our findings suggest that submaximal short duration activities (and tests) statistically reduce the voltage of ST segment, but, these depressions are not pathologically significant, because they were less than 0.1 mv.
Autoclaved Leishmania major vaccine for prevention of visceral leishmaniasis: a randomised, double-blind, BCG-controlled trial in Sudan
Authors: EAG Khalil, AMEl Hassan, EE Zijlstra, MM Mukhtar, HW Ghalib, Breyma Musa, ME Ibrahim, Areeg A Kamil, M Elsheikh, A Babiker, F Modabber
Journal: The Lancet (2000)
Expression patterns of microRNAs associated with CML phases and their disease related targets
Authors: Kateřina Machová Poláková, Tereza Lopotová, Hana Klamová, Pavel Burda, Marek Trněný, Tomáš Stopka, Jana Moravcová
Journal: Molecular Cancer (2011)

Abstract Background MicroRNAs are important regulators of transcription in hematopoiesis. Their expression deregulations were described in association with pathogenesis of some hematological malignancies. This study provides integrated microRNA expression profiling at different phases of chronic myeloid leukemia (CML) with the aim to identify microRNAs associated with CML pathogenesis. The functions of in silico filtered targets are in this report annotated and discussed in relation to CML pathogenesis. Results Using microarrays we identified differential expression profiles of 49 miRNAs in CML patients at diagnosis, in hematological relapse, therapy failure, blast crisis and major molecular response. The expression deregulation of miR-150, miR-20a, miR-17, miR-19a, miR-103, miR-144, miR-155, miR-181a, miR-221 and miR-222 in CML was confirmed by real-time quantitative PCR. In silico analyses identified targeted genes of these miRNAs encoding proteins that are involved in cell cycle and growth regulation as well as several key signaling pathways such as of mitogen activated kinase-like protein (MAPK), epidermal growth factor receptor (EGFR, ERBB), transforming growth factor beta (TGFB1) and tumor protein p53 that are all related to CML. Decreased levels of miR-150 were detected in patients at diagnosis, in blast crisis and 67% of hematological relapses and showed significant negative correlation with miR-150 proved target MYB and with BCR-ABL transcript level. Conclusions This study uncovers microRNAs that are potentially involved in CML and the annotated functions of in silico filtered targets of selected miRNAs outline mechanisms whereby microRNAs may be involved in CML pathogenesis.
Identification of a Nuclear Orphan Receptor (Ear2) as a Negative Regulator of Renin Gene Transcription
Authors: Xuebo Liu, Xiaodong Huang, Curt D. Sigmund
Journal: Circulation Research (2003)

A potent transcriptional enhancer was previously identified upstream of the mouse renin gene. Within the enhancer is a TGACCT direct-repeat motif, required for enhancer activity, that is the consensus sequence recognized by members of the thyroid hormone subfamily of steroid hormone receptors. We previously reported that RAR/RXR bind to this sequence and mediate the induction of renin promoter activity by retinoids. However, gel mobility shift assays clearly show that other as yet unidentified factors also bind to this motif. In order to identify some of these TGACCT binding factors, we screened a yeast one-hybrid cDNA library derived from mouse As4.1 cells. One of these encoded the orphan nuclear receptor Ear2. Recombinant Ear2 was purified from Escherichia coli and an antipeptide antisera was generated. EMSA showed that purified recombinant Ear2 specifically binds the TGACCT direct-repeat motif. Transfection assays showed that Ear2 potently decreases both baseline and retinoid-induced mouse renin promoter activity in a dose-dependent, enhancer-dependent, and sequence-specific manner. Mutations in Ear2, which abolish its binding to the TGACCT motif, also abolish transcriptional repression. Ear2 was identified as a nuclear protein in As4.1 cells, is one of the proteins binding to the TGACCT repeat motif, and its overexpression can repress transcription of the endogenous renin gene in As4.1 cells. These data suggest that Ear2 is a negative modulator of renin gene transcription in As4.1 cells, and that the renin enhancer may actually encode a complex positive and negative regulator of transcription.
Annual check-ups aren't needed, US study says
Authors: Janice Hopkins Tanne
Journal: BMJ (2007)

Annual physical examinations, a staple of medical care in the United States for decades, cost too much and are not necessary for conveying messages on preventing illness, says a new study. 

Patients get most messages on prevention through other visits, explains the study, published in the Archives of Internal Medicine (2007;167:1876-83). But annual gynaecological exams may be helpful for women, it says.

Ateev Mehrotra and colleagues from the University of Pittsburgh Medical Center examined data from 2002, 2003, and 2004 from the US national ambulatory medical care survey and the national hospital ambulatory medical care survey, which record visits made by patients with health …