nils-herrmann/clean_scirepeval huggingface dataset:
Histone acetylase and deacetylase activity in alveolar macrophages and blood mononocytes in asthma.

Histone acetylation status is a key factor in the regulation of inflammatory gene transcription. We investigated the activity of histone acetylases (HAT) and deacetylases (HDAC), and the effect of glucocorticoids in alveolar macrophages (AM) and peripheral blood mononuclear cells (PBMC) from subjects with asthma. Bronchoalveolar lavage was performed in 10 patients with intermittent asthma, 8 with persistent asthma, and 10 healthy control subjects. PBMCs and granulocytes were isolated from six patients with mild and severe asthma, before and after a 7-day course of prednisolone (30 mg/day). AMs were isolated for HDAC assay or incubated with dexamethasone (1 microM). HAT activity was increased (1.43 +/- 0.1 vs. 1.01 +/- 0.1 standard units/10 microg, p < 0.05), and HDAC activity was reduced (3031 +/- 243 vs. 5004 +/- 164 arbitrary fluorescence units/10 microg, p < 0.001) in AMs of subjects with asthma compared with control subjects. Dexamethasone suppressed LPS-induced granulocyte macrophage-colony stimulating factor, tumor necrosis factor-alpha, and interleukin-8 release by 83 +/- 1%, 51 +/- 7% and 20 +/- 9% (p < 0.001), respectively. Similar effects were seen on nuclear factor-kappaB inhibition, and interleukin-8 release was further reduced by the HDAC enhancer, theophylline (37 +/- 6%). Prednisolone increased HDAC activity in PBMCs from subjects with mild asthma. The increased inflammatory response in asthma may be due to reduced HDAC and enhanced HAT activity. Glucocorticoids and theophylline may downregulate the inflammatory response by modulating HAT and HDAC activity, and nuclear factor-kappaB activation.
Epstein-Barr virus DNA load in chronic lymphocytic leukemia is an independent predictor of clinical course and survival

The relation between Epstein-Barr virus (EBV) DNA load and clinical course of patients with chronic lymphocytic leukemia (CLL) is unknown. We assessed EBV DNA load by quantitative PCR at CLL presentation in mononuclear cells (MNC) of 220 prospective patients that were enrolled and followed-up in two major Institutions. In 20 patients EBV DNA load was also assessed on plasma samples. Forty-one age-matched healthy subjects were tested for EBV DNA load on MNC. Findings were validated in an independent retrospective cohort of 112 patients with CLL. EBV DNA load was detectable in 59%, and high (≥2000 copies/µg DNA) in 19% of patients, but it was negative in plasma samples. EBV DNA load was significantly higher in CLL patients than in healthy subjects (P < .0001). No relation was found between high EBV load and clinical stage or biological variables, except for 11q deletion (P = .004), CD38 expression (P = .003), and NOTCH1 mutations (P = .05). High EBV load led to a 3.14-fold increase in the hazard ratio of death and to a shorter overall survival (OS; P = .001). Poor OS was attributable, at least in part, to shorter time-to-first-treatment (P = .0008), with no higher risk of Richter's transformation or second cancer. Multivariate analysis selected high levels of EBV load as independent predictor of OS after controlling for confounding clinical and biological variables. EBV DNA load at presentation is an independent predictor of OS in patients with CLL.
Randomized , Double-Blind , Placebo-Controlled , Dose-Escalating Study of Aerosolized Interferon Gamma-1 b in Patients With Mild to Moderate Cystic Fibrosis Lung Disease

Interferon gamma-1b (IFN-g1b) is a pleiotropic cytokine with immunomodulatory activities that could decrease bacterial burden, inflammation, and obstruction in patients with CF. Patients with CF ( 12 years old, FEV1 40% predicted) were randomly assigned to sequential dose cohorts inhaling 500 mg IFN-g1b, 1,000 mg IFN-g1b, or placebo by Respirgard II nebulizer thrice weekly for 12 weeks. Sputum bacterial density and spirometry were measured. Safety, antibiotic use, hospitalization, and sputum neutrophils, elastase, DNA, IL-8, and myeloperoxidase were also evaluated. Sixty-six patients (mean age, 24 years, with mean baseline FEV1 of 74 20 (SD)percentpredicted)werestudied.Onepatient hadbronchospasmafter the first doseof IFN-g1b; the overall withdrawal rate was 15% (5 in the placebo group, 2 in the 500-mg IFN-g1b group, and 3 in the 1,000 mg IFN-g1b group). The 500-mg IFN-g1b dose waswell-tolerated, but the 1,000-mg dose cohort, who had a higher baseline bacterial density than placebo patients (mean difference, 1.2 log10 CFU/g sputum, 95% confidence interval (CI), 0.1,2.8, P1⁄40.04), had 24% more hospitalizations for exacerbation than placebo patients (95% CI, 2,45%, P1⁄40.05). There was a 0.12-l difference between the 500-mg IFN-g1b and placebo groups with respect to the
Impact of atrial fibrillation termination site and termination mode in catheter ablation on arrhythmia recurrence.

Although atrial fibrillation (AF) termination has been reported as a predictor of clinical outcome after persistent AF (PsAF) ablation, the relationship between AF termination site and mode and clinical outcome has not been fully evaluated.



A total of 135 patients (62±9 years) underwent their first ablation procedure for PsAF (76 longstanding PsAF). With an endpoint of AF termination, the ablation procedure was performed sequentially in the following order: pulmonary vein (PV) antrum isolation, and left atrial and right atrial substrate modification. AF termination was achieved in 69 patients (51%; 24 at the PV antrum, and 45 in the atrium; direct conversion to sinus rhythm in 21, and atrial tachycardia [AT] in 48). With a mean of 1.7±0.7 procedures/patient, 100 patients (74%) were free from atrial tachyarrhythmia (ATa) during a median of 15.0 months of follow-up. During the initial procedure, the AF termination site (atrium vs. PV antrum, hazard ratio [HR], 1.38; 95% confidence interval [CI]: 0.72-3.77; no termination vs. PV antrum, HR, 2.32; 95% CI: 1.26-6.30; P=0.023) and mode (AT vs. sinus rhythm, HR, 1.47; 95% CI: 0.77-4.01; no termination vs. sinus rhythm, HR, 2.38; 95% CI: 1.26-6.46; P=0.017) were independent predictors of ATa recurrence after the last ablation procedure.



The site and mode of AF termination during the index ablation procedure predict ATa recurrence following multiple catheter ablation procedures for PsAF.
Asthma control measurement using five different questionnaires: a prospective study.

Questionnaires play a key place in the assessment of asthma control. Different questionnaires have been developed. However, it remains largely unknown whether they can be used interchangeably. We wondered whether the panel of frequently used scores would give similar measurement of asthma control. The present study aimed to assess the agreement between five specific questionnaires.



In this prospective study, ninety-nine patients completed five commonly used asthma control scores: the GINA, the Asthma Control Test™, the Royal College of Physician score, the Asthma Therapy Assessment Questionnaire (ATAQ), and the Asthma Control Questionnaire(©) (ACQ). The kappa coefficient was used to assess the agreement between questionnaires.



The agreement between the GINA and other scores was only moderate (kappa coefficients amounted from 0.41 to 0.60). With respect to the "controlled" level, all the other scores gave higher results than GINA. All other scores also tended to underestimate GINA "uncontrolled level". For the "partly controlled level" defined by 3 of the 5 questionnaires, ACQ identified the same percentage of patients than GINA while ATAQ overestimated this percentage.



This study shows only moderate agreement between five commonly used asthma control scores. The GINA score showed the lowest percentage of controlled and the highest percentage of uncontrolled asthma. As a consequence, all these scores do not seem to evaluate the same symptoms.
Montelukast reduces airway eosinophilic inflammation in asthma: a randomized, controlled trial.

Leukotrienes are pro-inflammatory mediators which may contribute to tissue, sputum, and blood eosinophilia seen in allergic and inflammatory diseases, including asthma. Montelukast is a cysteinyl leukotriene1 (CysLT1) receptor antagonist which improves asthma control; the aim of this study was to investigate its effect on induced sputum eosinophils. Montelukast 10 mg (n=19) or placebo (n=21) were administered orally once in the evening for 4 weeks to 40 chronic adult asthmatic patients, aged 19-64 yrs, in a double-blind, randomized, parallel group study. Patients were included if, at prestudy, they had >5% sputum eosinophils, symptomatic asthma with a forced expiratory volume in one second > or =65% of the predicted value and were being treated only with "as needed" inhaled beta2-agonists. In addition to sputum eosinophils, blood eosinophils and clinical endpoints were also assessed. Four weeks of montelukast treatment decreased sputum eosinophils from 7.5% to 3.9% (3.6% decrease, 95% confidence interval (CI) -16.6-0.4). In contrast, placebo treatment was associated with an increase in sputum eosinophils from 14.5% to 17.9% (3.4% increase, 95% CI -3.5-9.8). The least squares mean difference between groups (-11.3%, 95% CI -21.1-(-1.4)) was significant (p=0.026). Compared with placebo, montelukast significantly reduced blood eosinophils (p=0.009), asthma symptoms (p=0.001) and beta2-agonist use (p<0.001) while significantly increasing morning peak expiratory flow (p=0.001). Montelukast was generally well tolerated in this study, with a safety profile similar to the placebo. These results demonstrate that montelukast decreases airway eosinophilic inflammation in addition to improving clinical parameters. Its efficacy in the treatment of chronic asthma may be due, in part, to the effect on airway inflammation.
Neurologic features of Hutchinson-Gilford progeria syndrome after lonafarnib treatment.

The objective of this study was to retrospectively evaluate neurologic status pre- and posttreatment with the oral farnesyltransferase inhibitor lonafarnib in children with Hutchinson-Gilford progeria syndrome (HGPS), a rare, fatal disorder of segmental premature aging that results in early death by myocardial infarction or stroke.



The primary outcome measure for intervention with lonafarnib was to assess increase over pretherapy in estimated annual rate of weight gain. In this study, neurologic signs and symptoms were compared pre- and posttreatment with lonafarnib.



Twenty-six participants were treated for a minimum of 2 years. Frequency of clinical strokes, headaches, and seizures was reduced from pretrial rates. Three patients with a history of frequent TIAs and average clinical stroke frequency of 1.75/year during the year before treatment experienced no new events during treatment. One patient with a history of stroke died due to large-vessel hemispheric stroke after 5 months on treatment. Headache prevalence and frequency were reduced. Four patients exhibited pretherapy seizures and no patients experienced recurrent or new-onset seizures.



This study provides preliminary evidence that lonafarnib therapy may improve neurologic status of children with HGPS. To address this question, we have incorporated prospective neuroimaging and neurologic assessments as measures in subsequent studies involving children with HGPS.



This study provides Class IV evidence that lonafarnib 115-150 mg/m(2) for 24 to 29 months reduces the prevalence of stroke and TIA and the prevalence and frequency of headache over the treatment period.
Phase I and Pharmacokinetic Trial of the Proapoptotic Sulindac Analog CP-461 in Patients with Advanced Cancer 1

CP-461 is a member of a class of novel proapoptotic drugs that specifically inhibit cyclic GMP phosphodiesterases but not cyclooxygenase-1 or -2. CP-461 inhibits the growth of a broad range of human tumor cell lines in vitro at micromolar concentrations and selectively induces apoptosis in cancer cell lines but not normal cells. Preclinical studies revealed good oral bioavailability and no toxicity in dogs and rats at single doses up to 500 mg/kg. In a Phase I trial, 21 patients with a range of solid tumors and good performance status received CP-461 p.o. twice daily for 28 consecutive days. Cycles were repeated without a treatment-free interval. CP-461 doses ranged from 100 to 800 mg/day. Therapy was well tolerated overall, and a maximum tolerated dose was not reached. Grade 3 asymptomatic aspartate aminotransferase/alanine aminotransferase elevation in 1 patient treated at 800 mg/day was the only dose-limiting toxicity. No hematologic toxicity was noted. Peak plasma concentrations occurred between 1 and 2 h after dosing, and doses above 200 mg/day exceeded the known in vitro EC50 (1–2 M) for apoptosis in cancer cells. No drug was detectable after 24 h of administration, and the terminal half-life was 6.7 h. The area under the plasma concentration-time curve was dose-proportional from 200 to 800 mg/day. Four patients exhibited disease stability after two cycles of treatment. CP-461 is minimally toxic at doses up to 800 mg/day when administered p.o. on a twice-daily schedule.
Heritability of high sugar consumption through drinks and the genetic correlation with substance use.

High sugar consumption contributes to the rising prevalence of obesity. Sugar can have rewarding effects that are similar to, but less strong than, the effects of addictive substances. People who consume large amounts of sugar also tend to use more addictive substances, but it is unclear whether this is due to shared genetic or environmental risk factors.



We examined whether there are genetic influences on the consumption of sugar-containing drinks and whether genetic factors can explain the association with substance use.



The frequency of consumption of sugar-containing drinks (e.g., cola, soft drinks, and energy drinks) and addictive substances (nicotine, caffeine, alcohol, cannabis, and illicit drugs) was obtained for 8586 twins who were registered at the Netherlands Twin Register (women: 68.7%; mean ± SD age: 33.5 ± 15.3 y). Participants were categorized as high or low sugar consumers (>1 compared with ≤1 SD above daily consumption in grams) and as high or low substance users (≥2 compared with <2 substances). Through bivariate genetic modeling, genetic and environmental influences on sugar consumption, substance use, and their association were estimated.



Genetic factors explained 48% of the variation in high sugar consumption, whereas unique environmental factors explained 52%. For high substance use, these values were 62% and 38%, respectively. There was a moderate phenotypic association between high sugar consumption and high substance use (r = 0.2), which was explained by genetic factors (59%) and unique environmental factors (41%).



The positive association between high sugar consumption and high substance use was partly due to unique environmental factors (e.g., social situations). Genetic factors were also of influence, suggesting that neuronal circuits underlying the development of addiction and obesity are related. Further research is needed to identify genes that influence sugar consumption and those that overlap with substance use.
Validation of the Brazilian version of the neurological fatigue index for multiple sclerosis.

The Neurological Fatigue Index for Multiple Sclerosis (NFI-MS) is a new fatigue assessment instrument. The aim of this study was to cross-culturally adapt and assess the psychometric properties of the Brazilian version of the NFI-MS (NFI-MS/BR).



Two hundred and forty subjects with MS were recruited for this study. The adaptation of the NFI-MS was performed by translation and back translation methodology. In psychometric analysis was performed the administration of the questionnaires Epworth Sleep Scale, Fatigue Severity Scale, Modified Fatigue Impact Scale, Multiple Sclerosis Impact Scale-29, NFI-MS/BR and Pittsburgh Sleep Quality Index with retest of the NFI-MS/BR after 7 days.



Reliability was assessed (intraclass correlation coefficients between 0.77 and 0.86), and validity by testing 41 hypotheses about expected correlations between subscales and confirmed 36. The majority of correlations were demonstrated.



The NFI-MS/BR is a cross-culturally adapted, valid, and reliable instrument for assessing MS fatigue among Brazilian subjects.
Effect of long-term interactive music therapy on behavior profile and musical skills in young adults with severe autism.

Data on the potential behavioral effects of music therapy in autism are scarce.



The aim of this study was to investigate whether a musical training program based on interactive music therapy sessions could enhance the behavioral profile and the musical skills of young adults affected by severe autism.



Young adults (N = 8) with severe (Childhood Autism Rating Scale >30) autism took part in a total of 52 weekly active music therapy sessions lasting 60 minutes. Each session consisted of a wide range of different musical activities including singing, piano playing, and drumming. Clinical rating scales included the Clinical Global Impression (CGI) scale and the Brief Psychiatric Rating Scale (BPRS). Musical skills-including singing a short or long melody, playing the C scale on a keyboard, music absorption, rhythm reproduction, and execution of complex rhythmic patterns-were rated on a 5-point Likert-type scale ranging from "completely/entirely absent" to "completely/entirely present."



At the end of the 52-week training period, significant improvements were found on both the CGI and BPRS scales. Similarly, the patients' musical skills significantly ameliorated as compared to baseline ratings.



Our pilot data seem to suggest that active music therapy sessions could be of aid in improving autistic symptoms, as well as personal musical skills in young adults with severe autism.
Abnormal Motor Cortex Excitability in Congenital Stroke

The aim of the present study was to investigate corticospinal and intracortical excitability in patients with congenital stroke. In adults, stroke sequelae reduce corticospinal excitability, as indicated by an elevated threshold for motor evoked potentials (MEP), and increase intracortical excitability, as indicated by reduced intracortical inhibition. Ten patients with pre- or perinatally acquired, unilateral cortico-subcortical infarctions in the middle cerebral artery territory were studied with single pulse transcranial magnetic stimulation (TMS) to measure motor threshold (MT) and with paired pulse TMS to study short interval intracortical inhibition (SICI) and intracortical facilitation (ICF). Eight healthy, age-matched subjects served as controls. MT over the affected hemisphere of patients compared with the dominant hemisphere of controls was significantly elevated, reflecting reduced corticospinal excitability, and SICI was significantly reduced, reflecting increased intracortical excitability. No such differences were found for ICF. Findings in patients with congenital stroke were comparable with adulthood stroke. Thus, similar assumptions can be made: reduced corticospinal excitability is probably a consequence of neuronal damage. Reduced intracortical inhibition might represent deficient inhibitory cortical properties or might reflect a compensational mechanism, dispositioning for use-dependent plasticity.
Effect of inhaled inactivated Mycobacterium phlei in children with moderate asthma.

Bacillus Calmette-Guérin and other mycobacterial vaccines are important therapeutic methods in a series of chronic inflammatory disorders characterized by Th1/Th2 imbalance in which Th2 type cells and cytokines often increase. However, few studies have investigated whether it can reduce or prevent the symptoms and attacks in children with asthma. This study evaluated the effect of inactivated Mycobacterium phlei inhaled by an atomizing device placed on asthmatic children. In this randomized, single-center, Seretide-controlled study, children aged 4-12 years with newly diagnosed, moderate, persistent asthma were treated with either inhaled inactivated M. phlei or inhaled Seretide patch. The efficacy of inhaled inactivated M. phlei was related with the alleviation of asthma symptoms, improvement of lung function and reduction of bronchial hyper-responsiveness and total serum IgE, which was similar with Seretide. These findings may have important clinical value in confirming inhaled inactivated M. phlei as a new therapeutic method in moderately asthmatic children.
Two Dosing Regimens of Certolizumab Pegol in Patients With Active Rheumatoid Arthritis

To investigate clinical efficacy and safety of 2 certolizumab pegol (CZP) maintenance dosing regimens plus methotrexate (MTX) in active rheumatoid arthritis (RA) patients achieving the American College of Rheumatology 20% improvement criteria (ACR20) after the CZP 200 mg every 2 weeks open-label run-in period.



DOSEFLEX (dosing flexibility) was a double-blind, placebo-controlled randomized study with an open-label run-in phase. During the run-in phase, all patients received CZP 400 mg (weeks 0, 2, and 4) and 200 mg every 2 weeks to week 16. Week 16 ACR20 responders were randomized 1:1:1 at week 18 to CZP 200 mg every 2 weeks, 400 mg every 4 weeks, or placebo.



A total of 209 (of 333) patients were randomized at week 18 (CZP: 200 mg, n = 70; 400 mg, n = 70; placebo, n = 69). Groups had similar baseline characteristics (week 0). Week 34 ACR20 response rates were comparable between the CZP 200 mg every 2 weeks and the 400 mg every 4 weeks groups (67.1% versus 65.2%), which was significantly higher than placebo (44.9%; P = 0.009 and P = 0.017). ACR50/70 and remission criteria were met more frequently in CZP groups than placebo at week 34, with similar responses between anti-tumor necrosis factor-experienced and naive patients. Improvements from baseline Disease Activity Score in 28 joints using the erythrocyte sedimentation rate and Health Assessment Questionnaire disability index scores were maintained in CZP groups from week 16 to 34 while worsening on placebo. Adverse event (AE) rates in the double-blind phase were 62.9% versus 60.9% versus 62.3%; serious AE rates were 7.1% versus 2.9% versus 0.0% (CZP 200 mg, 400 mg, and placebo groups).



In active RA patients with an incomplete MTX response, CZP 200 mg every 2 weeks and 400 mg every 4 weeks were comparable and better than placebo for maintaining clinical response to week 4 following a 16-week, open-label run-in phase.
Application of rigid motion geometry to historical film restoration

Historical film restoration involves locating the position of artifacts and replacing the ”missing” portion of the film (obscured by the artifact) with pixels that had been lost. Computer vision research has recently developed many techniques for constraining and predicting parts of a scene based upon the assumption of rigid motion. In this paper, we show how the constraints can help identify artifacts as well as how the prediction can be used to replace the artefact with natural looking portions of the scene. These techniques can be superior, when the rigid motion assumption is valid, to other techniques for historical film restoration.
A comparison of the antihypertensive effect of atenolol (ICI 66 082) and propranolol

Propranolol was given to 30 patients with essential hypertension following randomised, double-blind administration of either placebo or a new cardioselective beta-adrenergic receptor antagonist, atenolol (Tenormin®, ICI 66 082). Both atenolol and propranolol caused statistically significant reduction of recumbent and erect blood pressure and heart rate. There were no important differences between these variables on comparison of atenolol and propranolol.