tbuckley/cabot-search huggingface dataset:
Finding exonic islands in a sea of non-coding sequence: splicing related constraints on protein composition and evolution are common in intron-rich genomes
Authors: Tobias Warnecke, Joanna L Parmley, Laurence D Hurst
Journal: Genome biology (2008)

In mammals, splice-regulatory domains impose marked trends on the relative abundance of certain amino acids near exon-intron boundaries. Is this a mammalian particularity or symptomatic of exonic splicing regulation across taxa? Are such trends more common in species that a priori have a harder time identifying exon ends, that is, those with pre-mRNA rich in intronic sequence? We address these questions surveying exon composition in a sample of phylogenetically diverse genomes. Biased amino acid usage near exon-intron boundaries is common throughout the metazoa but not restricted to the metazoa. There is extensive cross-species concordance as to which amino acids are affected, and reduced/elevated abundances are well predicted by knowledge of splice enhancers. Species expected to rely on exon definition for splicing, that is, those with a higher ratio of intronic to coding sequence, more introns per gene and longer introns, exhibit more amino acid skews. Notably, this includes the intron-rich basidiomycete Cryptococcus neoformans, which, unlike intron-poor ascomycetes (Schizosaccharomyces pombe, Saccharomyces cerevisiae), exhibits compositional biases reminiscent of the metazoa. Strikingly, 5 prime ends of nematode exons deviate radically from normality: amino acids strongly preferred near boundaries are strongly avoided in other species, and vice versa. This we suggest is a measure to avoid attracting trans-splicing machinery. Constraints on amino acid composition near exon-intron boundaries are phylogenetically widespread and characteristic of species where exon localization should be problematic. That compositional biases accord with sequence preferences of splice-regulatory proteins and are absent in ascomycetes is consistent with selection on exonic splicing regulation.
Ethical issues in qualitative research on internet communities
Authors: G. Eysenbach, J. E Till
Journal: BMJ (2001)

The internet is the most comprehensive electronic archive of written material representing our world and peoples' opinions, concerns, and desires.Physicians who surf the internet for the first time are often stunned by what they learn on websites set up by lay people or patient self support communities.Material on these venues can be a rich source for researchers interested in understanding the experiences and views of people and patients.Qualitative analysis of material published and communicated on the internet can serve to systematise and codify needs, values, concerns, and preferences of consumers and professionals relevant to health and health care.While the internet makes people's interactions uniquely accessible for researchers and erases boundaries of time and distance, such research raises new issues in research ethics, particularly concerning informed consent and privacy of research subjects, as the borders between public and private spaces are sometimes blurred.
Improved health outcomes in patients with COPD during 1 yr's treatment with tiotropium
Authors: W. Vincken, J.A. van Noord, A.P.M. Greefhorst, Th.A. Bantje, S. Kesten, L. Korducki, P.J.G. Cornelissen
Journal: European Respiratory Journal (2002)

Tiotropium, a novel once-daily inhaled anticholinergic, has been shown to improve lung function over a 24-h period. In order to extend these findings, health-outcomes were evaluated over 1 yr in chronic obstructive pulmonary disease (COPD) patients. Spirometric results, peak expiratory flow rate (PEFR), salbutamol use and effects on dyspnoea, health-related quality of life and COPD exacerbations were assessed in two identical 1-yr randomized double-blind double-dummy studies of tiotropium 18µg once daily (n=356) compared with ipratropium 40µg q.i.d. (n=179). Screening forced expiratory volume in one second (FEV 1 ) were 1.25±0.43 L (41.9±12.7% of the predicted value) (tiotropium) and 1.18±0.37 L (39.4±10.7% pred) (ipratropium). Trough FEV 1 at 1 yr improved by 0.12±0.01 L with tiotropium and declined by 0.03±0.02 L with ipratropium (p&lt;0.001). Significant improvement in PEFR, salbutamol use, Transition Dyspnea Index focal score, and the St George's Respiratory Questionnaire total and impact scores were seen with tiotropium (p&lt;0.01). Tiotropium reduced the number of exacerbations (by 24%, p&lt;0.01), and increased time to first exacerbation (p&lt;0.01) and time to first hospitalization for a COPD exacerbation (p&lt;0.05) compared with ipratropium. Apart from an increased incidence of dry mouth in the tiotropium group, adverse events were similar between treatments. Tiotropium was effective in improving dyspnoea, exacerbations, health-related quality of life and lung function in patients with chronic obstructive pulmonary disease, and exceeds the benefits seen with ipratropium. The data support the use of tiotropium once-daily as first-line maintenance treatment in patients with chronic obstructive pulmonary disease.
Guillain-Barre syndrome and adjuvanted pandemic influenza A (H1N1) 2009 vaccine: multinational case-control study in Europe
Authors: J. Dieleman, S. Romio, K. Johansen, D. Weibel, J. Bonhoeffer, M. Sturkenboom
Journal: BMJ (2011)

<b>Objective</b> To assess the association between pandemic influenza A (H1N1) 2009 vaccine and Guillain-Barré syndrome. <b>Design</b> Case-control study. <b>Setting</b> Five European countries. <b>Participants</b> 104 patients with Guillain-Barré syndrome and its variant Miller-Fisher syndrome matched to one or more controls. Case status was classified according to the Brighton Collaboration definition. Controls were matched to cases on age, sex, index date, and country. <b>Main outcome measures</b> Relative risk estimate for Guillain-Barré syndrome after pandemic influenza vaccine. <b>Results</b> Case recruitment and vaccine coverage varied considerably between countries; the most common vaccines used were adjuvanted (Pandemrix and Focetria). The unadjusted pooled risk estimate for all countries was 2.8 (95% confidence interval 1.3 to 6.0). After adjustment for influenza-like illness/upper respiratory tract infection and seasonal influenza vaccination, receipt of pandemic influenza vaccine was not associated with an increased risk of Guillain-Barré syndrome (adjusted odds ratio 1.0, 0.3 to 2.7). The 95% confidence interval shows that the absolute effect of vaccination could range from one avoided case of Guillain-Barré syndrome up to three excess cases within six weeks after vaccination in one million people. <b>Conclusions</b> The risk of occurrence of Guillain-Barré syndrome is not increased after pandemic influenza vaccine, although the upper limit does not exclude a potential increase in risk up to 2.7-fold or three excess cases per one million vaccinated people. When assessing the association between pandemic influenza vaccines and Guillain-Barré syndrome it is important to account for the effects of influenza-like illness/upper respiratory tract infection, seasonal influenza vaccination, and calendar time.
Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1
Authors: Salima Hacein-Bey-Abina, Alexandrine Garrigue, Gary P. Wang, Jean Soulier, Annick Lim, Estelle Morillon, Emmanuelle Clappier, Laure Caccavelli, Eric Delabesse, Kheira Beldjord, Vahid Asnafi, Elizabeth MacIntyre, Liliane Dal Cortivo, Isabelle Radford, Nicole Brousse, François Sigaux, Despina Moshous, Julia Hauer, Arndt Borkhardt, Bernd H. Belohradsky, Uwe Wintergerst, Maria C. Velez, Lily Leiva, Ricardo Sorensen, Nicolas Wulffraat, Stéphane Blanche, Frederic D. Bushman, Alain Fischer, Marina Cavazzana-Calvo
Journal: Journal of Clinical Investigation (2008)

Previously, several individuals with X-linked SCID (SCID-X1) were treated by gene therapy to restore the missing IL-2 receptor gamma (IL2RG) gene to CD34+ BM precursor cells using gammaretroviral vectors. While 9 of 10 patients were successfully treated, 4 of the 9 developed T cell leukemia 31-68 months after gene therapy. In 2 of these cases, blast cells contained activating vector insertions near the LIM domain-only 2 (LMO2) proto-oncogene. Here, we report data on the 2 most recent adverse events, which occurred in patients 7 and 10. In patient 10, blast cells contained an integrated vector near LMO2 and a second integrated vector near the proto-oncogene BMI1. In patient 7, blast cells contained an integrated vector near a third proto-oncogene,CCND2. Additional genetic abnormalities in the patients' blast cells included chromosomal translocations, gain-of-function mutations activating NOTCH1, and copy number changes, including deletion of tumor suppressor gene CDKN2A, 6q interstitial losses, and SIL-TAL1 rearrangement. These findings functionally specify a genetic network that controls growth in T cell progenitors. Chemotherapy led to sustained remission in 3 of the 4 cases of T cell leukemia, but failed in the fourth. Successful chemotherapy was associated with restoration of polyclonal transduced T cell populations. As a result, the treated patients continued to benefit from therapeutic gene transfer.
Long-Term Neurological Outcome of Childhood Brain Tumors Treated by Surgery Only
Authors: Signe Sønderkær, Marianne Schmiegelow, Henrik Carstensen, Lars Bøgeskov Nielsen, Jørn Müller, Kjeld Schmiegelow
Journal: Journal of Clinical Oncology (2003)

To evaluate the pattern of neurological late effects in patients who have received surgery only for a brain tumor in childhood and to identify possible risk factors for neurological sequelae.The medical, histologic, and operative records were reviewed for 65 consecutive patients operated for a benign brain tumor from 1970 to 1997, and all patients were re-examined after a median length of follow-up of 10.7 years. Thirty-four patients had posterior fossa tumors, 22 patients had cerebral hemisphere tumors, and nine patients had midline tumors.At the time of follow-up, 20 patients (31%) had no neurological deficits, 22 patients (34%) had minor deficits that did not interfere with their daily life activities, and 23 patients (35%) had moderate or severe deficits such as severe ataxia, spastic paresis, seriously reduced vision, or epilepsy with more than two seizures per year. Fourteen of the 31 patients (45%) registered with ataxia preoperatively had recovered fully. Six of seven patients had persistence of a pre- or postoperatively developed hemiparesis. Thirteen of 23 patients had persistence of cranial nerve deficits that developed second to surgery. Fifty-five percent of the 18 patients with seizures at diagnosis were seizure-free at follow-up. At follow-up both ataxia and hemiparesis were significantly more frequent among females (P =.02 and P =.03, respectively).In patients who received operation as the only treatment for their brain tumor, there was a good chance of total or partial recovery of preoperative and postoperative neurological deficits, although only one third of the patients will have no long-term neurological deficits.
EFFECT OF ADMISSION ORAL DIURETIC DOSE ON RESPONSE TO CONTINUOUS VERSUS BOLUS INTRAVENOUS DIURETICS IN ACUTE HEART FAILURE: AN ANALYSIS FROM DOSE-AHF
Authors: Ravi V. Shah, Steven McNulty, Kerry Lee, G. Michael Felker, Christopher M. O'Connor, Michael M. Givertz
Journal: Journal of the American College of Cardiology (2011)
Environmental Tobacco Smoke, Genetic Susceptibility, and Risk of Lung Cancer in Never-Smoking Women
Authors: W. P. Bennett, M. C. R. Alavanja, B. Blomeke, K. H. Vahakangas, K. Castren, J. A. Welsh, E. D. Bowman, M. A. Khan, D. B. Flieder, C. C. Harris
Journal: JNCI Journal of the National Cancer Institute (1999)

Exposure to environmental tobacco smoke (ETS) is considered to be a major lung cancer risk factor for never smokers. We investigated the hypothesis that never-smoking women who are exposed to ETS and develop lung cancer are a genetically susceptible population.Archival tumor tissues were analyzed from 106 never-smoking women enrolled in a case-control study of ETS (and other personal and environmental factors) and lung cancer risk. We analyzed germline polymorphisms in genes that have been associated with cancer susceptibility and whose products activate (cytochrome P450 1A1 [CYP1A1]) and detoxify (glutathione S-transferases M1 [GSTM1] and T1 [GSTT1]) chemical carcinogens found in tobacco smoke.When compared with never smokers who had no ETS exposure and developed lung cancer (n = 55), never smokers with exposure to ETS who developed lung cancer (n = 51) were more likely to be deficient in GSTM1 activity (i.e., were GSTM1 null) because of a genetic polymorphism in the GSTM1 gene (odds ratio = 2.6; 95% confidence interval = 1.1-6.1). A statistically significant rising trend in risk occurred with increasing ETS exposure (two-sided P =. 02), reaching a more than sixfold excess risk in those exposed to 55 pack-years of ETS (ETS pack-year = ETS produced by an active smoker, within a confined space such as a room, who smokes one pack of cigarettes a day for a year). No evidence was found of associations between GSTT1 deficiency or the CYP1A1 valine variant and lung cancer risk due to ETS exposure.A common genetic polymorphism divides the population of never smokers into two groups of approximately equal size, one (homozygous carriers of the GSTM1 null allele) that has a statistically significant greater risk of lung cancer from ETS than the other (heterozygous or homozygous carriers of the wild-type GSTM1 allele).
A3.17 Clinical and therapeutic description of a serie of patients with immune thrombocytopenia.
Authors: LM Jimenez Liñan, R Sánchez Hernández, ML Feijoo Velloso, de la Fuente JL Marenco
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Immune thrombocytopenia (ITP) is characterised by a low platelet count and an increased risk of bleeding. Rheumatologist usually diagnosed ITP associated with systemic lupus erythematosus (SLE) but patients not always meet criteria. <h3>Objectives</h3> To describe clinical features and treatment in a series of patients with ITP. <h3>Patients and Methods</h3> We identified 11 patients with ITP and made a description of our experience. <h3>Results</h3> The mean age was 38.1 ± 12 years (81.8% female) with a and mean disease duration of 9.18 ± 4.68 years. Four of the 11 patients had some bleeding, being metrorrhagia the most common. The median platelet count in the diagnosis was 42,763 ± 23221/microL, and actually 147800 ± 136144/microL. Nine of the 11 patients had positive ANA (none of them antiDNA), 72.7% presented hypocomplementemia and antiphospholipid antibodies were present in only 2 patients. Eight of the 11 patients did not meet criteria for SLE. All the patients received glucocorticoids. The 63.6% were treated with azathioprine and/or hydroxychloroquine. Intravenous immunoglobulin were used in 3 patients. Three patients underwent splenectomy. Rituximab was used in 2 patients. Two patients ANA + had a platelet count below 10000/microL without bleeding. One was treated with corticosteroids and hydroxychloroquine achieving a platelet count of 70000/microL, and the other one with azathioprine, rituximab and splenectomy with normal levels of platelets actually. The 3 patients with diagnosis of SLE, have a mean number of platelets in the diagnosis of 53266.66 ± 15362.73, and despite treatment with glucocorticoids, hydroxychloroquine, azathioprine and rituximab in 2 of then (positive for antiphospholipids antibody) had the worst results with a median platelet count actually of 48333.33 ± 26764.4 <h3>DISCUSSION</h3> Patients with ITP can be very heterogeneous. Most of them can9t be classified as SLE. The pathogenesis of ITP is based on the combination of increased platelet destruction and inhibition of platelet production by essentially autoantibodies against GPIIb / III, but in SLE and especially with antiphospholipid antibodies, must be other associated mechanisms such as increased platelet consumption by thrombotic microangiopathy, that can modified treatment response. Further studies with more patients would be necessary to analyse the differences in SLE and no SLE patients with ITP.
Clinical Characteristics of Type II Diabetic Subjects Consuming High Versus Low Carbohydrate Diets in Mexico City and San Antonio, Texas
Authors: Clicerio Gonzélez, Michael P Stern, Braxton D Mitchell, Rodolfo A Valdez, Steven M Haffner, Beatriz Arredondo Pérez
Journal: Diabetes Care (1994)

OBJECTIVE To compare the clinical status of type II diabetic subjects identified in two population-based surveys, one performed in Mexico City, Mexico and the other in San Antonio, Texas. RESEARCH DESIGN AND METHODS In a low income area of Mexico City, 3,517 age-eligible (35–64 years of age) individuals were randomly selected of whom 3,319 were interviewed at home and 2,198 were examined in a clinic (response rates 62.5%). In San Antonio, 2,357 similarly aged low-income Mexican Americans were randomly selected of whom 2,076 were interviewed at home and 1,511 were examined (response rate 64.1%). Oral glucose tolerance tests were performed at both sites and diabetes was diagnosed according to the World Health Organization (WHO) criteria. In Mexico City, 288 type II diabetic individuals were identified, and 255 were identified in San Antonio. The following variables were measured: height, weight, subscapular and triceps skinfolds, waist-to-hip circumference ratios (WHR), systolic and diastolic blood pressure (random 0 sphygmomanometer), fasting and 2-h postglucose load glucose and insulin concentrations, and fasting total-cholesterol, HDL-cholesterol, and triglyceride (TG) levels. A food frequency questionnaire was used to estimate total calories and the percentage of calories derived from protein, fat, and carbohydrate. Only type II diabetic patients were included in the analyses. Age-adjustment was performed by analysis of covariance for continuous variables and by the Mantel-Haenszel procedure for discrete variables. RESULTS The mean age, the percentage newly diagnosed cases, and the percentage of males were similar in both sites. The percentage of diabetic patients treated with oral agents was significantly higher in Mexico City (56.9 vs. 72.7% in San Antonio and Mexico City, respectively, P &amp;lt; 0.001), whereas the percentage treated with insulin was significantly higher in San Antonio (18.8 vs. 2.1% for San Antonio and Mexico City, respectively, P &amp;lt; 0.001). A significant difference was observed in the percentage of calories derived from carbohydrate (61.7–63.2 vs. 47.1–47.5% for Mexico City and San Antonio, respectively, P &amp;lt; 0.001) and fat (18.4–20.0 and 30.1–33.0% for Mexico City and San Antonio, respectively, P &amp;lt; 0.001). Body mass index (BMI)
Sleep Need: How Much Sleep and What Kind?
Authors: ERNEST HARTMANN, FREDERICK BAEKELAND, GEORGE ZWILLING, PATRICK HOY
Journal: American Journal of Psychiatry (1971)

The authors studied 29 healthy men who habitualy slept nocturnally for long or short periods. The short sleepers were efficient, hardworking, and somewhat hypomanic: the long sleepers tended to be anxious, depressed, and withdrawn. Both groups had similar slow-wave-sleep (SWS) time, but the long sleepers had twice as much D (REM) sleep. The authors suggest that there are two separate requirements—a relatively constant requirement for SWS and a requirement for D sleep that is related to the individual's personality and life style.
Optimism, Cynical Hostility, and Incident Coronary Heart Disease and Mortality in the Women’s Health Initiative
Authors: Hilary A. Tindle, Yue-Fang Chang, Lewis H. Kuller, JoAnn E. Manson, Jennifer G. Robinson, Milagros C. Rosal, Greg J. Siegle, Karen A. Matthews
Journal: Circulation (2009)

Trait optimism (positive future expectations) and cynical, hostile attitudes toward others have not been studied together in relation to incident coronary heart disease (CHD) and mortality in postmenopausal women.Participants were 97 253 women (89 259 white, 7994 black) from the Women's Health Initiative who were free of cancer and cardiovascular disease at study entry. Optimism was assessed by the Life Orientation Test-Revised and cynical hostility by the cynicism subscale of the Cook Medley Questionnaire. Cox proportional hazard models produced adjusted hazard ratios (AHRs) for incident CHD (myocardial infarction, angina, percutaneous coronary angioplasty, or coronary artery bypass surgery) and total mortality (CHD, cardiovascular disease, or cancer related) over approximately 8 years. Optimists (top versus bottom quartile ["pessimists"]) had lower age-adjusted rates (per 10 000) of CHD (43 versus 60) and total mortality (46 versus 63). The most cynical, hostile women (top versus bottom quartile) had higher rates of CHD (56 versus 44) and total mortality (63 versus 46). Optimists (versus pessimists) had a lower hazard of CHD (AHR 0.91, 95% CI 0.83 to 0.99), CHD-related mortality (AHR 0.70, 95% CI 0.55 to 0.90), cancer-related mortality (blacks only; AHR 0.56, 95% CI 0.35 to 0.88), and total mortality (AHR 0.86, 95% CI 0.79 to 0.93). Most (versus least) cynical, hostile women had a higher hazard of cancer-related mortality (AHR 1.23, 95% CI 1.09 to 1.40) and total mortality (AHR 1.16, 95% CI 1.07 to 1.27; this effect was pronounced in blacks). Effects of optimism and cynical hostility were independent.Optimism and cynical hostility are independently associated with important health outcomes in black and white women. Future research should examine whether interventions designed to change attitudes would lead to altered risk.
Ulcer recurrence after in-hospital treatment for recalcitrant venous leg ulceration
Authors: S. Reeder, K.-P. de Roos, M. de Maeseneer, A. Sommer, H.A.M. Neumann
Journal: British Journal of Dermatology (2012)

Leg ulceration caused by chronic venous disease occurs in 1% of the adult Western population. A majority of these patients is successfully treated in the outpatient setting. A minority of patients is hospitalized, most frequently because of the lack of healing tendency. The literature provides recurrence rates for ulcer disease, but lacks specific data on recurrence rates after in-hospital treatment of recalcitrant venous leg ulcers.To investigate time to ulcer recurrence after in-hospital treatment of venous leg ulceration.A multicentre, retrospective cohort study of patients admitted for leg ulceration between 1996 and 2007 was conducted.Data could be collected for 107 of the patients. Of these, 27 had conservative treatment (bed rest, local wound care, pain management) and 48 patients underwent surgical ulcer treatment with (n = 19) or without (n = 29) initial vacuum-assisted closure (VAC) treatment. The treatment method was 'miscellaneous' in the remaining 32 patients. Median admission time was 30 days, median percentage of closure at discharge was 95%, and median time to ulcer recurrence 60 days. The Mann-Whitney U-test showed significant differences between the conservative group and the surgery group, the latter having a longer length of hospital stay (P < 0.0001) and a higher percentage of ulcer closure (P < 0.0001), but there was no difference in time to ulcer recurrence (P = 0.273). Comparable differences were demonstrated between the conservative group and the VAC plus surgery group. No significant differences could be demonstrated between the surgically treated patients and those treated by VAC and surgery.Hospital stay is significantly shorter in cases of surgical treatment of recalcitrant venous leg ulcers. Most ulcers recur within 2 months after hospital discharge. Recurrence of venous leg ulcers after hospital admission is independent of the method of treatment and cause of ulceration.