tbuckley/cabot-search huggingface dataset:
Sense-antisense pairs in mammals: functional and evolutionary considerations
Authors: Pedro AF Galante, Daniel O Vidal, Jorge E de Souza, Anamaria A Camargo, Sandro J de Souza
Journal: Genome biology (2007)

A significant number of genes in mammalian genomes are being found to have natural antisense transcripts (NATs). These sense-antisense (S-AS) pairs are believed to be involved in several cellular phenomena.Here, we generated a catalog of S-AS pairs occurring in the human and mouse genomes by analyzing different sources of expressed sequences available in the public domain plus 122 massively parallel signature sequencing (MPSS) libraries from a variety of human and mouse tissues. Using this dataset of almost 20,000 S-AS pairs in both genomes we investigated, in a computational and experimental way, several putative roles that have been assigned to NATs, including gene expression regulation. Furthermore, these global analyses allowed us to better dissect and propose new roles for NATs. Surprisingly, we found that a significant fraction of NATs are artifacts produced by genomic priming during cDNA library construction.We propose an evolutionary and functional model in which alternative polyadenylation and retroposition account for the origin of a significant number of functional S-AS pairs in mammalian genomes.
Inhaled Colistin in Patients with Bronchiectasis and Chronic <i>Pseudomonas aeruginosa</i> Infection
Authors: Charles S. Haworth, Juliet E. Foweraker, Peter Wilkinson, Robert F. Kenyon, Diana Bilton
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Chronic infection with Pseudomonas aeruginosa is associated with an increased exacerbation frequency, a more rapid decline in lung function, and increased mortality in patients with bronchiectasis.
The coronary circulation in cardioprotection: more than just one confounder
Authors: G. Heusch, P. Kleinbongard, A. Skyschally, B. Levkau, R. Schulz, R. Erbel
Journal: Cardiovascular Research (2011)

Cardioprotection, i.e. the reduction in infarct size by pre-, post-, or remote conditioning, has originally been characterized in young and healthy experimental animals. Over the last two decades many signalling steps of cardioprotection have been identified, again in young and healthy animals. Although proof-of-concept studies unequivocally demonstrated the recruitment of all forms of cardioprotection in humans, the translation of cardioprotection to clinical routine has been poor. The apparent lack of translation has been attributed to poor design of clinical trials, but also to the neglect of confounders, such as age, sex, comorbidities, and comedications, in experimental studies. The present opinionated review focuses on the coronary circulation as a major determinant of cardioprotection. Coronary occlusion and the restoration of coronary blood flow are the causes of myocardial ischaemia and reperfusion injury from which protection is sought. On the other hand, brief cycles of coronary occlusion and reperfusion are also the stimulus for protection from myocardial ischaemia/reperfusion injury. The recruitment of collateral blood flow also contributes to protection from infarction. Finally, the coronary microcirculation is also a target of both injury by myocardial ischaemia/reperfusion and protection from it. Different manifestations of coronary artery disease, such as coronary stenosis or coronary microembolization, impact on both injury and protection.
Using Pharmacokinetic and Pharmacodynamic Data in Early Decision Making Regarding Drug Development: A Phase I Clinical Trial Evaluating Tyrosine Kinase Inhibitor, AEE788
Authors: José Baselga, Alain C. Mita, Patrick Schöffski, Herlinde Dumez, Frederico Rojo, Josep Tabernero, Clifford DiLea, William Mietlowski, Christie Low, Jerry Huang, Margaret Dugan, Kathryn Parker, Eric Walk, Allan van Oosterom, Erika Martinelli, Chris H. Takimoto
Journal: Clinical Cancer Research (2012)

In this first-in-human study of AEE788, a tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR), HER-2, and VEGFR-2, a comprehensive pharmacodynamic program was implemented in addition to the evaluation of safety, pharmacokinetics, and preliminary efficacy of AEE788 in cancer patients.Patients with advanced, solid tumors received escalating doses of oral AEE788 once daily. Primary endpoints were to determine dose-limiting toxicities (DLTs) and maximum-tolerated dose (MTD). A nonlinear model (Emax model) was used to describe the relationship between AEE788 exposure and target-pathway modulation in skin and tumor tissues.Overall, 111 patients were treated (25 to 550 mg/day). DLTs included rash and diarrhea; MTD was 450 mg/day. Effects on biomarkers correlated to serum AEE788 concentrations. The concentration at 50% inhibition (IC(50)) for EGFR in skin (0.033 μmol/L) and tumor (0.0125 μmol/L) were similar to IC(50) in vitro suggesting skin may be surrogate tissue for estimating tumor EGFR inhibition. No inhibition of p-MAPK and Ki67 was observed in skin vessels at ≤ MTD. Hence, AEE788 inhibited EGFR, but not VEGFR, at doses ≤ MTD. A total of 16 of 96 evaluable patients showed a >10% shrinkage of tumor size; one partial response was observed.Our pharmacodynamic-based study showed effective inhibition of EGFR, but not of VEGFR at tolerable AEE788 doses. Emax modeling integrated with biomarker data effectively guided real-time decision making in the early development of AEE788. Despite clinical activity, target inhibition of only EGFR led to discontinuation of further AEE788 development.
Clustering of hand osteoarthritis progression and its relationship to progression of osteoarthritis at the knee
Authors: Jessica Bijsterbosch, Ingrid Meulenbelt, Iain Watt, Frits R Rosendaal, Tom W J Huizinga, Margreet Kloppenburg
Journal: Annals of the Rheumatic Diseases (2013)

To investigate patterns of osteoarthritis (OA) progression within hand joints and the relationship between hand OA progression and progression of OA at the knee.Radiographic progression over 6 years, defined as change in osteophytes or joint space narrowing above the smallest detectable change, was assessed on hand and knee radiographs of 236 hand OA patients participating in the Genetics, Arthrosis and Progression (GARP) sibling pair cohort study using OARSI atlas. Clustering of radiographic progression between hand joint groups (DIP, PIP, IP-1 and CMC-1) was assessed using χ(2) test. Symmetry, clustering by row and ray and familial aggregation in sibling pairs were also evaluated. The association between hand OA progression and progression of OA at the knee was assessed using generalised estimating equation analysis.There was clustering of OA progression between hand joint groups, the strongest relationship among DIP, PIP and IP-1 joints. Other patterns were symmetry (OR 4.7 (95% CI 3.3 to 6.5)) and clustering by row (OR 2.9 (95% CI 1.9 to 4.6)) but not by ray (OR 1.3 (95% CI 0.7 to 2.4)). There was familial aggregation of hand OA progression. Patients with progression of hand OA had a higher risk for radiographic change at the knee than those without hand OA progression (OR 2.3 (95% CI 1.3 to 4.0)).Progression of hand OA clusters between hand joint groups, especially between IP joints, and within sibling pairs. It is associated with OA change at the knee. These findings contribute to defining hand OA subsets and suggest a role for systemic factors.
Intensive Insulin Therapy in Severely Burned Pediatric Patients
Authors: Marc G. Jeschke, Gabriela A. Kulp, Robert Kraft, Celeste C. Finnerty, Ron Mlcak, Jong O. Lee, David N. Herndon
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Hyperglycemia and insulin resistance have been shown to increase morbidity and mortality in severely burned patients, and glycemic control appears essential to improve clinical outcomes. However, to date no prospective randomized study exists that determines whether intensive insulin therapy is associated with improved post-burn morbidity and mortality.To determine whether intensive insulin therapy is associated with improved post-burn morbidity.A total of 239 severely burned pediatric patients with burns over greater than 30% of their total body surface area were randomized (block randomization 1:3) to intensive insulin treatment (n = 60) or control (n = 179).Demographics, clinical outcomes, sepsis, glucose metabolism, organ function, and inflammatory, acute-phase, and hypermetabolic responses were determined. Demographics were similar in both groups. Intensive insulin treatment significantly decreased the incidence of infections and sepsis compared with controls (P < 0.05). Furthermore, intensive insulin therapy improved organ function as indicated by improved serum markers, DENVER2 scores, and ultrasound (P < 0.05). Intensive insulin therapy alleviated post-burn insulin resistance and the vast catabolic response of the body (P < 0.05). Intensive insulin treatment dampened inflammatory and acute-phase responses by deceasing IL-6 and acute-phase proteins compared with controls (P < 0.05). Mortality was 4% in the intensive insulin therapy group and 11% in the control group (P = 0.14).In this prospective randomized clinical trial, we showed that intensive insulin therapy improves post-burn morbidity. Clinical trial registered with www.clinicaltrials.gov (NCT00673309).
Metabolism of Endogenous Surfactant in Premature Baboons and Effect of Prenatal Corticosteroids
Authors: JAN ERIK H. BUNT, VIRGILIO P. CARNIELLI, STEVEN R. SEIDNER, MACHIKO IKEGAMI, J. L. DARCOS WATTIMENA, PIETER J. J. SAUER, ALAN H. JOBE, LUC J. I. ZIMMERMANN
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

We studied the synthesis of surfactant and the effect of prenatal betamethasone treatment in vivo in very preterm baboons. Ten pregnant baboons were randomized to receive either betamethasone (beta) or saline (control) 48 and 24 h before preterm delivery. The newborn baboons were intubated, treated with surfactant, and ventilated for 6 d. They received a 24-h infusion with the stable isotope [U-13C]glucose as precursor for the synthesis of palmitic acid in surfactant phosphatidylcholine (PC). Palmitic acid in surfactant PC became enriched 27 ± 2 h after the start of the isotope infusion and was maximally enriched at 100 ± 4 h. The fractional synthesis rate of PC palmitate in the beta group (1.5 ± 0.2%/d) was increased by 129% above control (0.7 ± 0.1%/d) (p < 0.02, Mann– Whitney U test). The absolute synthesis rate of PC in the beta group [1.6 ± 0.3 μ mol/kg/d] was increased by 128% above controls [0.7 ± 0.2 μ mol/kg/d] (p < 0.02). These data show that the synthesis of endogenous surfactant from plasma glucose as precursor is a slow process. It is shown, for the first time in vivo, that prenatal glucocorticosteroids stimulate the synthesis of surfactant PC in the very premature baboon. Bunt JEH, Carnielli VP, Seidner SR, Ikegami M, Wattimena JLD, Sauer PJJ, Jobe AH, Zimmermann LJI. Metabolism of endogenous surfactant in premature baboons and effect of prenatal corticosteroids.
Pro-arrhythmic and pro-ischaemic effects of inhaled anticholinergic medications
Authors: Sonal Singh, Yoon K Loke, Paul Enright, Curt D Furberg
Journal: Thorax (2012)

The majority of deaths in COPD are from cardiovascular causes. Several large randomized controlled trials demonstrate that inhaled anticholinergic agents ipratropium and tiotropium increase the risk of serious cardiovascular events, including cardiovascular mortality. Tiotropium Respimat is associated with a statistically significant increased risk of mortality (RR 1.52; 95% CI 1.06 to 2.16) and cardiovascular death (RR 2.05; 95% CI 1.06 to 3.99) compared with placebo in a meta-analysis of clinical trials. In the largest study, the subgroup of patients with COPD in the Respimat group with known rhythm and cardiac disorders at baseline had an especially high risk for cardiac death (RR 8.6; 95% CI 1.1 to 67.2). Although there was no significantly increased risk of mortality (HR 0.89; 95% CI 0.79 to 1.02) or myocardial infarction (MI) (RR 0.73; 95% CI 0.53 to 1.00) with tiotropium handihaler in the Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) trial, the reported excess of angina (RR 1.44; 95% CI 0.91 to 2.26), imbalance in strokes related to ischaemia and rates of supraventricular tachyarrhythmias are consistent with the pro-ischemic and pro-arrhythmic effects. The subjects at greatest risk of cardiovascular death, such as those with a recent history of MI, unstable or life-threatening cardiac arrhythmias or hospitalisation with heart failure, were excluded from the UPLIFT trial. The Prevention of Exacerbations with Tiotropium in COPD trial showed an excess of serious coronary ischaemic events of angina, myocardial ischaemia and MI with the tiotropium Handihaler compared with salmeterol. The authors urge caution in prescribing inhaled anticholinergics for patients with pre-existing arrhythmias or cardiac disorders.
ABC of nutrition. Measuring nutrition.
Authors: A S Truswell
Journal: BMJ (1985)

What is your appetite like?* Do you eat more or less than other comparable people?* Has what you eat changed-type offood or amount?* Are you on a special diet?* Is there any food you can't eat because it doesn't agree with you? * Are you losing or gaining in body weight?* What do you usually have for the main meal of the day?* Do you eat meat/fruit/fat on meat/salt/etc?* What sort ofbread do you eat? * What sort ofalcoholdo you drink, how many
Propensity for osteoarthritis and lower limb joint pain in retired professional soccer players
Authors: S Drawer, C W Fuller
Journal: British Journal of Sports Medicine (2001)

Objective —To quantify the prevalence of osteoarthritis and the severity of pain in the lower limb joints of players retired from English professional soccer. Method —An anonymous self administered questionnaire was distributed to 500 former players registered with the English Professional Footballers' Association. The questionnaire was designed to gather information on personal details, physical activity loading patterns, history of lower limb joint injury, and current medical condition of the lower limb joints. Results —Of 500 questionnaires distributed, 185 (37%) were returned. Nearly half of the respondents (79: 47%) retired because of injury; 42% (33) were acute injuries and 58% (46) chronic injuries. Most of the acute injuries that led to early retirement were of the knee (15: 46%), followed by the ankle (7: 21%) and lower back (5: 15%). Most of the chronic injuries that led to early retirement were also of the knee (17: 37%), followed by the lower back (10: 22%) and the hip (4: 9%). Of all respondents, 32% (59) had been medically diagnosed with osteoarthritis in at least one of the lower limb joints. More respondents had been diagnosed with osteoarthritis in the knee joints than either the ankle or the hip joints. Significantly (p&lt;0.001) more respondents reported pain in one lower extremity joint during one or more daily activities than those who did not (joint pain: 137, 80%; no joint pain: 35, 20%). Conclusion —The risk for professional soccer players of osteoarthritis in at least one of the lower extremity joints is very high and significantly greater than for the general population. The results support the suggestion that professional soccer players should be provided with health surveillance during their playing career.
Smoking and increased severity of hepatic fibrosis in primary biliary cirrhosis: A cross validated retrospective assessment
Authors: Claudia O. Zein, Kristi Beatty, Anthony B. Post, Laurie Logan, Sara Debanne, Arthur J. McCullough
Journal: Hepatology (2006)

An epidemiological association between cigarette smoking and primary biliary cirrhosis (PBC) has been demonstrated. Our aim was to determine the relationship between smoking and severity of liver fibrosis at presentation in patients with PBC. All patients with PBC seen at the three major teaching hospitals of Case Western Reserve University between October 1998 and December 2005 were identified. Data obtained at the time of the first evaluation leading to the PBC diagnosis on 97 patients were collected. The cumulative number of cigarette packs smoked per year (pack-years) was calculated. Advanced histological disease was defined as Ludwig stages 3 or 4. Analyses were performed to determine associations between advanced histological disease, smoking and other variables related to liver fibrosis. Smoking history was more common ( P = .0008) in patients with advanced histological disease at presentation compared to those with early disease. Among smokers, mean lifetime tobacco consumption was higher ( P = .04) in cases with advanced histological disease at presentation (30 pack-years) compared to cases with early disease (17 pack-years). Logistic regression demonstrated a significant association between a lifetime tobacco consumption of ≥10 pack-years and advanced histological disease at presentation (OR = 13.3). The association remained significant after adjusting for age, gender, and alcohol intake. The validity of these results was corroborated by cross-validation in an independent confirmatory set of 172 patients with PBC. In conclusion , smoking may accelerate the progression of PBC. This could be induced by exposure to chemicals in cigarette smoke.
Emergency management of an uncommon abdominal pain
Authors: C.-H. Lu, T.-C. Chang, P.-S. Lai, H.-J. Hsieh, K.-L. Liu
Journal: Gut (2010)

A 69-year-old man with medical history of hypercholesterolaemia presented to our emergency department with a 1-day history of abdominal pain. The pain was neither related to eating nor affected by position. There was no recent change in bowel habit. He was haemodynamically stable, but a palpable left abdominal mass was noted. Laboratory tests were within normal limits. An erect abdominal radiograph suggested small bowel loops clustered in the left side of abdomen (figure 1) but because of diagnostic uncertainty an urgent computed tomography (CT) scan was performed within 3 h on the …
Targeted Disruption of LIGHT Causes Defects in Costimulatory T Cell Activation and Reveals Cooperation with Lymphotoxin β in Mesenteric Lymph Node Genesis
Authors: Stefanie Scheu, Judith Alferink, Tobias Pötzel, Winfried Barchet, Ulrich Kalinke, Klaus Pfeffer
Journal: The Journal of Experimental Medicine (2002)

The recently described tumor necrosis factor (TNF) family member LIGHT (herpes virus entry mediator [HVEM]-L/TNFSF14), a ligand for the lymphotoxin (LT)β receptor, HVEM, and DcR3, was inactivated in the mouse. In contrast to mice deficient in any other member of the LT core family, LIGHT−/− mice develop intact lymphoid organs. Interestingly, a lower percentage of LIGHT−/−LTβ−/− animals contain mesenteric lymph nodes as compared with LTβ−/− mice, whereas the splenic microarchitecture of LIGHT−/−LTβ−/− and LTβ−/− mice shows a comparable state of disruption. This suggests the existance of an additional undiscovered ligand for the LTβ receptor (LTβR) or a weak LTα3–LTβR interaction in vivo involved in the formation of secondary lymphoid organs. LIGHT acts synergistically with CD28 in skin allograft rejection in vivo. The underlying mechanism was identified in in vitro allogeneic MLR studies, showing a reduced cytotoxic T lymphocyte activity and cytokine production. Detailed analyses revealed that proliferative responses specifically of CD8+ T cells are impaired and interleukin 2 secretion of CD4+ T cells is defective in the absence of LIGHT. Furthermore, a reduced 3[H]-thymidine incorporation after T cell receptor stimulation was observed. This for the first time provides in vivo evidence for a cooperative role for LIGHT and LTβ in lymphoid organogenesis and indicates important costimulatory functions for LIGHT in T cell activation.
Many sequence variants affecting diversity of adult human height
Authors: Daniel F Gudbjartsson, G Bragi Walters, Gudmar Thorleifsson, Hreinn Stefansson, Bjarni V Halldorsson, Pasha Zusmanovich, Patrick Sulem, Steinunn Thorlacius, Arnaldur Gylfason, Stacy Steinberg, Anna Helgadottir, Andres Ingason, Valgerdur Steinthorsdottir, Elinborg J Olafsdottir, Gudridur H Olafsdottir, Thorvaldur Jonsson, Knut Borch-Johnsen, Torben Hansen, Gitte Andersen, Torben Jorgensen, Oluf Pedersen, Katja K Aben, J Alfred Witjes, Dorine W Swinkels, Martin den Heijer, Barbara Franke, Andre L M Verbeek, Diane M Becker, Lisa R Yanek, Lewis C Becker, Laufey Tryggvadottir, Thorunn Rafnar, Jeffrey Gulcher, Lambertus A Kiemeney, Augustine Kong, Unnur Thorsteinsdottir, Kari Stefansson
Journal: Nature Genetics (2008)
A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan
Authors: Sebastian Brandhorst, In Young Choi, Min Wei, Chia Wei Cheng, Sargis Sedrakyan, Gerardo Navarrete, Louis Dubeau, Li Peng Yap, Ryan Park, Manlio Vinciguerra, Stefano Di Biase, Hamed Mirzaei, Mario G. Mirisola, Patra Childress, Lingyun Ji, Susan Groshen, Fabio Penna, Patrizio Odetti, Laura Perin, Peter S. Conti, Yuji Ikeno, Brian K. Kennedy, Pinchas Cohen, Todd E. Morgan, Tanya B. Dorff, Valter D. Longo
Journal: Cell Metabolism (2015)
Calcium metabolism in patients with epilepsy.
Authors: J. Bowe
Journal: BMJ (1970)

MEDICBUAAL 559were inserted into the fossa navicularis, approximately 10 mm. from the exterior.It may be significant that the swabs were transported in our mycoplasma transport medium, which contains yeast extract and 20% unheated horse serum,3 and were not frozen.We have frequently isolated H.S.V. from cervical swabs transported in nutrient broth, but it is possible that a higher number of isolations of H.S.V. might be achieved by using a transport medium enriched with serum.-Weare, etc.,
Changes in exhaled carbon monoxide and nitric oxide levels following allergen challenge in patients with asthma
Authors: P Paredi, MJ Leckie, I Horvath, L Allegra, SA Kharitonov, PJ Barnes
Journal: European Respiratory Journal (1999)

Carbon monoxide is a product of haem degradation by haem oxygenase (HO), activated by inflammatory cytokines and oxidants. This study examined whether allergen challenge can increase exhaled CO levels, as a reflection of HO activation. Exhaled CO and nitric oxide, an expired gas also thought to reflect cytokine-induced airway inflammation, were measured in 15 atopic steroid-naive nonsmoking patients with asthma (13 males, aged 30+/-2 yrs) before and for up to 20 h after allergen challenge. Baseline CO (4.4+/-0.3 parts per million (ppm)) and NO (20.6+/-1.2 parts per billion (ppb)) levels were elevated in asthmatic as compared with nonsmoking normal volunteers (n = 37, 2.1+/-0.2 ppm and 7.0+/-0.1 ppb, respectively, p&lt;0.05). In 10 patients with a dual response in the forced expiratory volume in one second (FEV1) there was a maximal increase in exhaled CO at 1 h (343+/-7.1%) and at 6 h (69+/-12%, p&lt;0.01), followed by a maximal fall in FEV1 (28+/-9%, p&lt;0.05) at 9 h, whereas the maximal NO increase was observed at 10 h (50.2+/-11.8%). The maximal increase in exhaled CO in single response patients (n = 5) was 30+/-2% during the early asthmatic reaction and 46.3+/-9.2% between 4 and 10 h, followed by a fall in FEV1 (9+/-3%, p&gt;0.05) at 9 h, whereas exhaled NO was not significantly changed. In five patients exhaled CO was not attenuated by inhalation of increasing concentrations of histamine causing a 20% fall in FEV1 (PC20) or its subsequent relief by beta2-agonists. In conclusion, exhaled carbon monoxide is increased during the early and late asthmatic reactions independently of the change in airway calibre, while exhaled nitric oxide is increased only during the late reaction and follows the increase in carbon monoxide and fall in the forced expiratory volume in one second in time.