tbuckley/cabot-search huggingface dataset:
Role of co-trimoxazole prophylaxis in reducing mortality in HIV infected adults being treated for tuberculosis: randomised clinical trial
Authors: A. J Nunn, P. Mwaba, C. Chintu, A. Mwinga, J. H Darbyshire, A. Zumla
Journal: BMJ (2008)

<h3>ABSTRACT</h3> HIV infection of the central nervous system causes HIV-associated neurocognitive disease (HAND) in up to 50% HIV-infected individuals. Cocaine use is prevalent in the HIV-infected population and has been shown to facilitate the HAND progression. However, the cellular and molecular mechanism of the cocaine-facilitated HAND progression remains largely unknown. In this study, we took advantage of the doxycycline inducible and brain-specific HIV Tat transgenic mouse model (iTat) of HAND and characterized effects of chronic cocaine exposure and long- term Tat expression on HAND-associated neurology and neuropathology. We found that cocaine exposure worsened the learning and memory of iTat mice, coupled with dendritic spine swelling, increased synaptophysin expression, and diminished microglia and astrocyte activation. We then employed the single-base resolution whole genome bisulfate sequencing and RNA sequencing and identified 14,838 hypermethylated CpG-related differentially methylated regions (DMR) and 15,800 hypomethylated CpG-related DMR that were linked to 52 down- and 127 up-regulated genes by cocaine and Tat. We further uncovered these genes to be mostly enriched at neuronal function- and cell morphology- and synapse formation-related <i>ECM-receptor interaction</i> pathway, and to be linked to behavioral and pathological changes altered by cocaine and Tat. Eight mostly affected genes included four in microglia <i>Ift172</i>, <i>Eif2ak4</i>, <i>Pik3c2a,</i> and <i>Phf8</i>, two in astrocytes <i>Garem1</i> and <i>Adgrb3</i>, and two in neurons <i>Dcun1d4</i> and <i>Adgrb3</i>. These findings demonstrated for the first time that cocaine and Tat interactively contributed to HAND neurology and neuropathology through genome-wide changes of DNA methylation and gene expression and suggest that targeting epigenetic changes serves as a potentially new therapeutic strategy to treat cocaine use disorder in people living with HAND.
SUMO-specific protease 7 (SENP7) regulates matrix metalloproteinase-9 expression in synovial fibroblasts
Authors: S Strietholt, M A Peters, S Frank, N Pundt, S Ender, G Kollias, T Pap
Journal: Annals of the Rheumatic Diseases (2010)

Small ubiquitin-related modifiers (SUMOs) are key players in post-translational protein modifications and regulate various cellular processes such as cell division or apoptosis. SUMOylation is regulated by a family of SUMO specific proteases (SENPs) known to activate SUMO precursors and regulate deSUMOylation processes of various target proteins. Our previous studies showed that enhanced SUMO expression in rheumatoid arthritis (RA) altered their apoptotic behaviour. Based on these findings and the fact that SENP7 is localised on a susceptibility locus …
The Cell Cycle Ontology: An application ontology for the representation and integrated analysis of the cell cycle process
Authors: Erick Antezana, Mikel Egana, Ward Blonde, Aitzol Illarramendi, Inaki Bilbao, Bernard De Baets, Robert Stevens, Vladimir Mironov, Martin Kuiper
Journal: Genome biology (2009)

The Cell Cycle Ontology ( http://www.CellCycleOntology.org ) is an application ontology that automatically captures and integrates detailed knowledge on the cell cycle process. Cell Cycle Ontology is enabled by semantic web technologies, and is accessible via the web for browsing, visualizing, advanced querying, and computational reasoning. Cell Cycle Ontology facilitates a detailed analysis of cell cycle-related molecular network components. Through querying and automated reasoning, it may provide new hypotheses to help steer a systems biology approach to biological network building.
Borrowing Information across Subgroups in Phase II Trials: Is It Useful?
Authors: Boris Freidlin, Edward L. Korn
Journal: Clinical Cancer Research (2013)

Abstract Because of the heterogeneity of human tumors, cancer patient populations are usually composed of multiple subgroups with different molecular and/or histologic characteristics. In screening new anticancer agents, there might be a scientific rationale to expect some degree of similarity in clinical activity across the subgroups. This poses a challenge to the design of phase II trials assessing clinical activity: Conducting an independent evaluation in each subgroup requires considerable time and resources, whereas a pooled evaluation that completely ignores patient heterogeneity can miss treatments that are only active in some subgroups. It has been suggested that approaches that borrow information across subgroups can improve efficiency in this setting. In particular, the hierarchical Bayesian approach putatively uses the outcome data to decide whether borrowing of information is appropriate. We evaluated potential benefits of the hierarchical Bayesian approach (using models suggested previously) and a simpler pooling approach by simulations. In the phase II setting, the hierarchical Bayesian approach is shown not to work well in the simulations considered, as there appears to be insufficient information in the outcome data to determine whether borrowing across subgroups is appropriate. When there is strong rationale for expecting a uniform level of activity across the subgroups, approaches using simple pooling of information across subgroups may be useful. Clin Cancer Res; 19(6); 1326–34. ©2012 AACR.
Right ventricular dysfunction in obstructive sleep apnoea: reversal with nasal continuous positive airway pressure
Authors: J Nahmias, R Lao, M Karetzky
Journal: European Respiratory Journal (1996)

The incidence and pathogenesis of right ventricular dysfunction in obstructive sleep apnoea (OSA) remains controversial. Using nuclear ventriculography, the prevalence of right ventricular dysfunction (RVD) was therefore determined in obese patients with OSA, as well as their clinical characteristics, arterial blood gas values, spirometry and sleep parameters. The reversibility of RVD was evaluated after long-term use of nasal continuous positive airway pressure (nCPAP). We studied 112 obese patients with OSA by nuclear ventriculography, 35 with RVD (Group 1), 77 without RVD (Group 2), and 14 patients without OSA as controls (Group 3). Repeat nuclear ventriculography was performed in seven patients who used nCPAP nightly for 6-24 months. The mean right ventricular ejection fractions (RVEF) were 31%, 47% and 44% in Groups 1, 2 and 3, respectively. Group 1 also had a lower left ventricular ejection fraction (LVEF) of 55 vs 63% in Group 2. The OSA groups did not differ in mean spirometric or arterial blood gas values. Group 1 had a lower mean nocturnal arterial oxygen saturation (Sa,O2) of 82 vs 87% in Group 2, and a longer apnoea duration of 22.3 vs 19.2 s. All but two patients in Group 1 had either awake alveolar hypoventilation or an apnoea + hypopnoea index > 40 disordered breathing events.h-1. Repeat nuclear ventriculography after nCPAP revealed an increase in RVEF from 30 to 39%. In conclusion, right ventricular dysfunction is common in obstructive sleep apnoea, but it is reversible with nasal continuous positive airway pressure treatment and appears to be related to nocturnal oxygen desaturation.
A human inhibitor of tumor necrosis factor alpha.
Authors: P Seckinger, S Isaaz, J M Dayer
Journal: The Journal of Experimental Medicine (1988)

Urine of some febrile patients exhibits a TNF-alpha inhibitory activity (TNF-alpha INH), sensitive to heat and trypsin, with an apparent mol wt of 40-60 X 10(3) and a pI range of 5.5-6.1. As for the Il-1 INH, the TNF INH activity involves a competitive mechanism of action suggesting the existence of a family of negative feedback-regulating molecules interfering with cytokines actions.
Serum selenium level and risk of lung cancer mortality: a 16-year follow-up of the Copenhagen Male Study
Authors: Poul Suadicani, Hans Ole Hein, Finn Gyntelberg
Journal: European Respiratory Journal (2011)

Serum selenium has been implicated as a risk factor for lung cancer, but the issue remains unsettled. In a cohort of 3,333 males aged 53-74 yrs, we tested the hypothesis that a low serum selenium concentration would be associated with an increased risk of lung cancer mortality. Over 16 yrs, 167 (5.1%) subjects died of lung cancer: 48 (5.0%) out of 965 with low serum selenium (0.4-1.0 μmol · L(-1)), 57 (5.1%) out of 1,141 with medium serum selenium (1.1-1.2 μmol · L(-1)) and 62 (5.1%) out of 1,227 with high serum selenium (1.3-3.0 μmol · L(-1)). After adjustment for age, referencing the lowest level of serum selenium, hazard ratios (HRs) for medium and high levels of serum selenium were 0.97 (95% CI 0.66-1.43) and 0.99 (95% CI 0.68-1.45), respectively. Taking into account pack-years of smoking, spirits intake, dietary markers (salt and fat preferences) and health measures (chronic bronchitis and peak flow), referencing the lowest level of serum selenium, HRs were 1.17 (95% CI 0.79-1.75) and 1.43 (95% CI 0.96-2.14), for medium and high levels respectively. Among heavy smokers, a high serum selenium concentration was associated with a significantly increased risk of lung cancer mortality after taking into account all potential confounders. The hypothesis that low serum selenium is an independent risk factor for lung cancer was not supported.
Cross-reactive lysis of trinitrophenyl (TNP)-derivatized H-2 incompatible target cells by cytolytic T lymphocytes generated against syngeneic TNP spleen cells.
Authors: S J Burakoff, R N Germain, B Benacerraf
Journal: The Journal of Experimental Medicine (1976)

Normal spleen cells, when cultured with irradiated trinitrophenyl (TNP)-derivatized syngeneic spleen cells, develop cytotoxic effectors that lyse most effectiviely a TNP-derivatized target that is H-2 compatible with the effector. However, these effectors also lyse to a lesser extent TNP tumor and TNP spleen targets that are H-2 incompatible. This cross-reactive lysis correlates with the degree of cytolysis seen on the TNP-derivatized syngeneic target; it appears to be medicated by Thy 1.2-bearing cells and is inhibited by antisera to the K and/or D loci of the target cell and not by antisera to non-K or non-D surface antigens. Nonradiolabeled TNP-derivatized lymphoid cells syngeneic to either the stimulator or the target are able to competitively inhibit cross-reactive lysis, while TNP chicken red blood cells are unable to specifically inhibit lysis. These data on cross-reactive lysis of TNP-conjugated targets are most consistent with the altered-self hypothesis.
T cell protein tyrosine phosphatase attenuates T cell signaling to maintain tolerance in mice
Authors: Florian Wiede, Benjamin J. Shields, Sock Hui Chew, Konstantinos Kyparissoudis, Catherine van Vliet, Sandra Galic, Michel L. Tremblay, Sarah M. Russell, Dale I. Godfrey, Tony Tiganis
Journal: Journal of Clinical Investigation (2011)

Many autoimmune diseases exhibit familial aggregation, indicating that they have genetic determinants. Single nucleotide polymorphisms in PTPN2, which encodes T cell protein tyrosine phosphatase (TCPTP), have been linked with the development of several autoimmune diseases, including type 1 diabetes and Crohn’s disease. In this study, we have identified TCPTP as a key negative regulator of TCR signaling, which might explain the association of PTPN2 SNPs with autoimmune disease. We found that TCPTP dephosphorylates and inactivates Src family kinases to regulate T cell responses. Using T cell–specific TCPTP-deficient mice, we established that TCPTP attenuates T cell activation and proliferation in vitro and blunts antigen-induced responses in vivo. TCPTP deficiency lowered the in vivo threshold for TCR-dependent CD8+ T cell proliferation. Consistent with this, T cell–specific TCPTP-deficient mice developed widespread inflammation and autoimmunity that was transferable to wild-type recipient mice by CD8+ T cells alone. This autoimmunity was associated with increased serum levels of proinflammatory cytokines and anti-nuclear antibodies, T cell infiltrates in non-lymphoid tissues, and liver disease. These data indicate that TCPTP is a critical negative regulator of TCR signaling that sets the threshold for TCR-induced naive T cell responses to prevent autoimmune and inflammatory disorders arising.
A randomised trial of ondansetron for the treatment of irritable bowel syndrome with diarrhoea
Authors: Klara Garsed, Julia Chernova, Margaret Hastings, Ching Lam, Luca Marciani, Gulzar Singh, Amanda P. Henry, Ian P. Hall, Peter Whorwell, Robin C. Spiller
Journal: Gut (2013)

<h3>Background</h3> Irritable bowel syndrome with diarrhoea (IBS-D) is particularly debilitating due to urgency and episodic incontinence. Some 5-hydroxytryptamine 3 (5-HT3) receptor antagonists (5-HT3RAs) have proven effective but have serious side effects. Ondansetron, also a 5-HT3RA, has been widely used as an antiemetic with an excellent safety record for over two decades. Our aim was to assess its effectiveness in IBS-D. <h3>Methods</h3> 120 patients meeting Rome III criteria for IBS-D entered a randomised, double-blind, placebo-controlled crossover study of 5 weeks of ondansetron 4 mg versus placebo with dose titration allowed, up to two tablets three times daily in the first 3 weeks. Patients completed daily diaries documenting stool consistency using the Bristol Stool Form score. Gut transit was measured in the last week of each treatment. The primary endpoint was average stool consistency in the last 2 weeks of treatment. <h3>Results</h3> Ondansetron significantly improved stool consistency (mean difference in stool form between ondansetron and placebo −0.9, 95% CI −1.1&nbsp;to −0.6, p&lt;0.001). Compared with placebo, patients on ondansetron experienced fewer days with urgency (p&lt;0.001), lower urgency scores (p&lt;0.001), reduced frequency of defaecation (p=0.002) and less bloating (p=0.002), although pain scores did not change significantly. IBS symptom severity score fell more with ondansetron than placebo (83±9.8 vs 37±9.7, p=0.001). 65% reported adequate relief with ondansetron but not placebo compared with 14% reporting relief with placebo but not ondansetron, relative risk 4.7, 95% CI 2.6 to 8.5, p&lt;0.001. <h3>Conclusions</h3> Ondansetron relieves some of the most intrusive symptoms of IBS-D, namely loose stools, frequency and urgency.
A longitudinal study of the effects of parental smoking on pulmonary function in children 6-18 years.
Authors: X Wang, D Wypij, D R Gold, F E Speizer, J H Ware, B G Ferris, D W Dockery
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

The association between parental cigarette smoking and children's pulmonary function was investigated in 8,706 nonsmoking white children, followed annually by questionnaire and spirometry between 6 and 18 yr. Exposure to maternal and paternal smoking was each divided into three components: exposure in the first 5 yr of life, cumulative exposure between age 6 and the year prior to each visit; parental smoking status reported at each visit. Regression splines were used to assess the effects of parental smoking on the level and growth rate of pulmonary function adjusting for age, height, city of residence, and parental education. Models best predicting pulmonary function level included current maternal smoking and exposure to maternal smoking in the first 5 yr of life but did not include the other measures of parental smoking. After adjusting for early exposure, current maternal smoking for each pack/d was associated with a reduced level of FEV1 (-0.4%, 95% CI: -0.9, 0.1), FEV1/FVC (-0.6%, 95% CI: -0.9, -0.4), and FEF25-75% (-2.3%, 95% CI: -3.6, -1.0) in children 6 to 10 yr. These effects were slightly smaller in children 11 to 18 yr. Adjusting for current maternal smoking, those exposed to maternal smoking in the first 5 yr of life had higher FVC (+0.5%, 95% CI: -0.1, 1.2) and lower FEV1/FVC (-0.7%, 95% CI: -1.1, -0.4) and FEF25-75% (-2.8%, 95% CI: -4.4, -1.2) than those not exposed in children 6 to 10 yr.(ABSTRACT TRUNCATED AT 250 WORDS)
FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study
Authors: Chiara Cremolini, Fotios Loupakis, Carlotta Antoniotti, Cristiana Lupi, Elisa Sensi, Sara Lonardi, Silvia Mezi, Gianluca Tomasello, Monica Ronzoni, Alberto Zaniboni, Giuseppe Tonini, Chiara Carlomagno, Giacomo Allegrini, Silvana Chiara, Mauro D'Amico, Cristina Granetto, Marina Cazzaniga, Luca Boni, Gabriella Fontanini, Alfredo Falcone
Journal: The Lancet Oncology (2015)
Abstract 675: Contrasting Effects of Dietary Carbohydrate Compared to Mono-unsaturated Fat on Hepatic Production of ApoE and ApoC-III Containing VLDL, and Formation of LDL
Authors: Chunyu Zheng, Christina Khoo, Frank M Sacks
Journal: Circulation (2007)

The effects of substituting dietary carbohydrate (CHO) with mono-unsaturated fat (MUFA) on plasma apoB metabolism were evaluated in 12 adults: 6 with normal and 6 with high plasma triglyceride levels. They consumed for 3 weeks each time a high CHO diet (48% complex CHO, 8% MUFA) and a high MUFA diet (31% complex CHO, 24% MUFA). ApoB100 kinetic studies were performed at the end of each dietary intervention using stable isotope labeling with a bolus and a primed continuous infusion. Multiple VLDL, IDL, and LDL fractions were prepared according to their apoE and apoC-III content. Compared to the CHO diet, the MUFA diet increased the percentage of VLDL and IDL secreted with both apoE and apoC-III (45% on MUFA vs. 14% on CHO, p &lt; 0.01) and reduced the percentage of VLDL and IDL secreted without either apoE or apoC-III (MUFA 19% vs. CHO 40%, p = 0.02). Total liver secretion rates of apoB100 lipoproteins were similar between diets (MUFA 11.6 vs. CHO 11.3 mg·day −1 ·kg −1 , p = NS). The dietary change did not affect the fractional catabolic rates and flux patterns of the lipoproteins. On both diets, VLDL and IDL that had apoE were rapidly cleared from the circulation, limiting LDL formation; whereas lipoproteins that did not have apoE or apoCIII mostly underwent lipolysis with little direct clearance, and were the main precursors of LDL. As a result, increased secretion of VLDL and IDL containing apoE and apoC-III caused by the MUFA diet was associated with higher direct clearance and lower LDL production rates (p = 0.02 vs. CHO), while the CHO diet increased LDL production due to increased secretion of VLDL without apoE or apoC-III. In conclusion, our results reveal a strong dietary effect on the secretion pattern of apoB100 lipoproteins. Substituting dietary complex carbohydrate with mono-unsaturated fat selectively promotes liver secretion of VLDL and IDL containing both apoE and apoC-III while suppressing the secretion of VLDL and IDL without apoE or apoC-III. This leads to significant downstream effects on LDL formation due to differential effects of apoE and apoC-III on apoB lipoprotein metabolism, resulting in enhanced particle clearance and reduced LDL formation with the MUFA diet compared to the CHO diet.
Variation of peak expiratory flow rate.
Authors: C K Connolly
Journal: Thorax (1981)

Variation of peak expiratory flow rate Sir,-In their article, Hetzel and Clark' suggest an amplitude of 20% in a 24-hour variation of peak ex- piratory flow rate should be regarded as a useful screening test for asthma.While I entirely sympathise with the view that the measurement of amplitude variation is one of the best ways of demonstrating variability of airway obstruction, this definition cer- tainly includes many patients who would be regarded as bronchitics without any evidence of asthma.In my paper,2 it was demonstrated that the mean amplitude of variation of bronchitis, measured in a different way, was well over 20 % before and over 20 % after bronchodilator.
Scientists unveil the next step in the human genome project
Authors: S. Gottlieb
Journal: BMJ (2002)

In an effort to speed up the search for the genes underlying diseases, Johns Hopkins University and an international consortium of scientists are embarking on a $100m (£64m; €100m) effort to create the next generation map of human DNA.

The venture, dubbed the international “HapMap” project, because it will map groups of genes known as haplotypes, is expected to take three years and involves public and private research centres in six countries. Its goal is to help scientists uncover the origins of complex diseases that have many genetic components, such as cancer, diabetes, and …
The potential benefits of outpatient investigations of suspected pulmonary embolism (PE)
Authors: Muhammad Josheel Naveed, P. Mchale, M. Gautam, Syed M.H. Kazmi, Colin Smyth, Hassan Burhan
Journal: European Respiratory Journal (2011)

Background:  Computed Tomography Pulmonary Angiography (CTPA) is the recommended investigation for non-massive pulmonary embolism (PE) and guidelines suggest outpatient management in stable patients with PE9 [1]. Outpatient investigation of such patients may also be potentially possible.   Aim:  To ascertain the proportion of patients admitted to our hospital with suspected PE that could potentially have been investigated as outpatients.   Methods:  Retrospective analysis of all CTPAs performed over an 8-week period from December 2009 in a UK university teaching hospital.   Results:  198 CTPA scans were performed. PE was confirmed in 30 (15.2%). The mean time period of inpatient stay before obtaining their CTPA was 5.5 days (SD 6).  51 (26%) patients were in hospital for    Conclusion:  A careful assessment to identify patients that can safely have an outpatient CTPA and decreasing time to scan for in-patients would increase efficiency.  A 20% reduction in time from admission to CTPA would result in an annual saving of 1290 bed days (approximately £410,000).  If we postulate that patients discharged ≤48 hours post CTPA were well enough to have been investigated as outpatients, doing so would have saved at least 288 bed days over 8 weeks, equating to 1728 bed days (£540,000) over a year.   Reference:   1British Thoracic Society PE Guidelines 2003.
Dermatitis during efalizumab treatment in a patient with psoriasis vulgaris
Authors: M. de Groot, M.A. de Rie, J.D. Bos
Journal: British Journal of Dermatology (2005)

Journal Article Dermatitis during efalizumab treatment in a patient with psoriasis vulgaris Get access M. De Groot, M. De Groot Department of Dermatology A0‐252, Academic Medical Centre, Meibergdreef 9, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands M. de Groot. E‐mail: m.degroot@amc.uva.nl Search for other works by this author on: Oxford Academic Google Scholar M.A. De Rie, M.A. De Rie Department of Dermatology A0‐252, Academic Medical Centre, Meibergdreef 9, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar J.D. Bos J.D. Bos Department of Dermatology A0‐252, Academic Medical Centre, Meibergdreef 9, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 153, Issue 4, 1 October 2005, Pages 843–844, https://doi.org/10.1111/j.1365-2133.2005.06840.x Published: 01 October 2005