nils-herrmann/clean_scirepeval huggingface dataset:
Baseline hepatitis B surface antigen (HBsAg) as predictor of sustained HBsAg loss in chronic hepatitis B patients treated with pegylated interferon-α2a and adefovir.

In this study, we aimed to identify baseline predictors of response in chronic hepatitis B patients treated with a combination of pegylated interferon (PEG-IFN)-α2a and adefovir.



We treated 92 chronic hepatitis B patients (44 hepatitis B e antigen [HBeAg]-positive and 48 HBeAg-negative) with HBV DNA > 100,000 copies/ml (> 17,182 IU/ml) with PEG-IFN and adefovir for 48 weeks and followed them up for 2 years. Baseline markers for HBeAg loss, combined response (HBeAg negativity, HBV DNA levels ≤ 2,000 IU/ml and alanine aminotransferase [ALT] normalization) and hepatitis B surface antigen (HBsAg) loss were evaluated.



Two years after the end of treatment, rates of HBeAg loss and HBsAg loss in HBeAg-positive patients were 18/44 (41%) and 5/44 (11%), respectively. In HBeAg-negative patients, rates of combined response and HBsAg loss were 12/48 (25%) and 8/48 (17%), respectively. HBeAg-negative patients with HBsAg loss had lower baseline HBsAg levels than those without HBsAg loss (mean HBsAg 2.35 versus 3.55 log10 IU/ml; P < 0.001). They also had lower HBV DNA levels and were more often (PEG-)IFN experienced. Baseline HBsAg was the only independent predictor of HBsAg loss (OR 0.02; P = 0.01).



With combination therapy of PEG-IFN and adefovir for 48 weeks, a high rate of HBsAg loss was observed in both HBeAg-positive (11%) and HBeAg-negative (17%) patients 2 years after treatment ended. In HBeAg-negative patients, a low baseline HBsAg level was a strong predictor for HBsAg loss.
Translating ceRNA Susceptibilities into Correlation Functions.

Competition to bind microRNAs induces an effective positive cross talk between their targets, which are therefore known as "competing endogenous RNAs" (ceRNAs). Although such an effect is known to play a significant role in specific situations, estimating its strength from data and experimentally in physiological conditions appears to be far from simple. Here, we show that the susceptibility of ceRNAs to different types of perturbations affecting their competitors (and hence their tendency to cross talk) can be encoded in quantities as intuitive and as simple to measure as correlation functions. This scenario is confirmed by extensive numerical simulations and validated by re-analyzing phosphatase and tensin homolog's cross-talk pattern from The Cancer Genome Atlas breast cancer database. These results clarify the links between different quantities used to estimate the intensity of ceRNA cross talk and provide, to our knowledge, new keys to analyze transcriptional data sets and effectively probe ceRNA networks in silico.
Soy isoflavones have an antiestrogenic effect and alter mammary promoter hypermethylation in healthy premenopausal women.

We determined if soy isoflavones have dose-related estrogenic and methylation effects. Thirty-four healthy premenopausal women were randomized to 40 mg or 140 mg isoflavones daily through one menstrual cycle. Breast specific and systemic estrogenic effects were assessed measuring the estrogenic marker complement (C)3 and changes in cytology, whereas methylation assessment of 5 cancer related genes (p16, RASSF1A, RARbeta2, ER, and CCND2) was performed on intraductal specimens. Serum genistein significantly increased after consuming both isoflavone doses. Cytology did not significantly change at either isoflavone dose. Serum C3 levels posttreatment were inversely related to change in serum genistein (r =-0.76, P = 0.0045) in women consuming low but not high dose isoflavones. The RAR beta 2 hypermethylation increase posttreatment correlated with the posttreatment genistein level considering the entire group (r = 0.67, P = 0.0017) and those receiving high-dose isoflavones (r = 0.68, P = 0.021). At the low but not the high isoflavone dose, CCND2 hypermethylation increase correlated with posttreatment genistein levels (r = 0.79, P = 0.011). In summary, the inverse correlation between C3 and genistein suggests an antiestrogenic effect. Isoflavones induced dose-specific changes in RARbeta2 and CCND2 gene methylation, which correlated with genistein levels. This work provides novel insights into estrogenic and methylation effects of dietary isoflavones.
Reliability and validity of bilateral ankle accelerometer algorithms for activity recognition and walking speed after stroke.

Outcome measures of mobility for large stroke trials are limited to timed walks for short distances in a laboratory, step counters and ordinal scales of disability and quality of life. Continuous monitoring and outcome measurements of the type and quantity of activity in the community would provide direct data about daily performance, including compliance with exercise and skills practice during routine care and clinical trials.



Twelve adults with impaired ambulation from hemiparetic stroke and 6 healthy controls wore triaxial accelerometers on their ankles. Walking speed for repeated outdoor walks was determined by machine-learning algorithms and compared to a stopwatch calculation of speed for distances not known to the algorithm. The reliability of recognizing walking, exercise, and cycling by the algorithms was compared to activity logs.



A high correlation was found between stopwatch-measured outdoor walking speed and algorithm-calculated speed (Pearson coefficient, 0.98; P=0.001) and for repeated measures of algorithm-derived walking speed (P=0.01). Bouts of walking >5 steps, variations in walking speed, cycling, stair climbing, and leg exercises were correctly identified during a day in the community. Compared to healthy subjects, those with stroke were, as expected, more sedentary and slower, and their gait revealed high paretic-to-unaffected leg swing ratios.



Test-retest reliability and concurrent and construct validity are high for activity pattern-recognition Bayesian algorithms developed from inertial sensors. This ratio scale data can provide real-world monitoring and outcome measurements of lower extremity activities and walking speed for stroke and rehabilitation studies.
A revised approach to patient selection for cardiac resynchronization treatment using multiple asynchrony parameters in Narrow- and Wide-QRS cardiomyopathy causes cardiac reverse remodelling: a single centre non-randomized prospective study.

Conflicting data exists on the benefit of cardiac resynchronization treatment (CRT) in patients with narrow QRS (Narrow-QRS) cardiomyopathy (CMP). We determined the effect of CRT in patients with CMP and mechanical asynchrony based on a comprehensive assessment by multiple echocardiographic criteria.



Ninety patients, 65 +/- 16 years, 32 with Narrow-QRS <120 ms and 58 with wide QRS >or=120 ms (Wide-QRS) CMP who met criteria for significant mechanical asynchrony by 15 criteria before CRT were studied. Responders were patients in whom end-systolic volume (ESV) reduced by >or=15% post-CRT. There was no difference in the response to CRT in the Narrow-QRS (ESV 132 +/- 60 to 120 +/- 60 mL, P = 0.02) or Wide-QRS (123 +/- 54 to 102 +/- 50 mL, P < 0.01) groups at 1 +/- 2 month follow-up. A difference of >or=40% in time to peak contraction in a cardiac cycle on tissue velocity imaging between the earliest and the most delayed segment had the best area under curve for response to CRT, 0.71 (0.55-0.85), P = 0.02. Using logistic regression model, delay in mid-posterolateral segment of >or=20% in a cardiac cycle compared with remaining 10 segments was the only predictor of response to CRT in the overall study population.  In patients with CMP and mechanical asynchrony by multiple criteria, response to CRT in Narrow-QRS group is similar to those with Wide-QRS. Greater than or equal to 40% delay in systolic contraction between 12 left ventricular (LV) segments or >or=20% delay of posterolateral segment to other LV segments predicted CRT response.
Phase I Trial of ISIS 5132, an antisense oligonucleotide inhibitor of c-raf-1, administered by 24-hour weekly infusion to patients with advanced cancer.

Raf-1 is a serine/threonine kinase that functions as a critical effector of Ras-mediated signal transduction via the mitogen-activated protein kinase pathway. Constitutive activation of this pathway directly contributes to malignant transformation in many human tumors. A 20-base phosphorothioate oligonucleotide complementary to c-raf-1 mRNA (ISIS 5132; CGP 69846A) has been shown to specifically suppress Raf-1 expression both in vitro and in vivo. This Phase I trial, involving 22 patients with advanced cancer, was designed to evaluate the safety, feasibility, and maximum tolerated dose of ISIS 5132 administration as a weekly 24-h i.v. infusion. Pharmacokinetic analysis was performed, and c-raf-1 mRNA levels in peripheral blood mononuclear cells were assessed using quantitative reverse transcription-PCR. This trial defined a maximum tolerated dose of 24 mg/kg/week on this schedule. Two of four patients treated at 30 mg/kg/week had serious adverse events after the first dose of ISIS 5132, including acute hemolytic anemia and acute renal failure and anasarca. There were no major responses documented. Dose-dependent complement activation was demonstrated on this schedule, but not on previously evaluated schedules, of ISIS 5132 administration. In contrast to other trials of ISIS 5132, there appeared to be no consistent suppression of peripheral blood mononuclear cell c-raf-1 mRNA level on this schedule at any of the dose levels analyzed. These data suggest that the efficacy and toxicity profiles of antisense oligonucleotides may be highly dependent on the schedule of administration and support the analysis of the putative molecular target in the evaluation of novel therapeutics.
Effect of rosuvastatin on plasma levels of asymmetric dimethylarginine in patients with hypercholesterolemia.

Elevated plasma levels of asymmetric dimethylarginine (ADMA) have been associated with attenuated endothelium-dependent vasodilation in hypercholesterolemic patients. However, whether lowering of plasma cholesterol concentration by hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) can reduce plasma ADMA levels is still not clear. This study was a multicenter, randomized, double-blind, placebo-controlled design including 46 patients with elevated low-density lipoprotein cholesterol levels. Patients were randomized into 2 groups: rosuvastatin 10 mg/day and placebo for 6 weeks. Plasma levels of ADMA, 8-isoprostane (as a marker of oxidative stress), homocysteine, and high-sensitivity C-reactive protein were measured at baseline and 6 weeks later. Endothelial function assessed by flow-mediated vasodilation of the brachial artery was performed in 11 patients in the rosuvastatin group and in 12 in the placebo group. Baseline characteristics of both groups were similar, and the plasma ADMA levels were significantly correlated with 8-isoprostane (r = 0.388, p = 0.008). After 6 weeks of treatment, plasma ADMA levels were significantly reduced in the rosuvastatin group (from 0.60 +/- 0.19 to 0.49 +/- 0.10 micromol/L, p <0.001). Increases in flow-mediated vasodilation were positively correlated with reductions in plasma levels of ADMA (p = 0.017) and low-density lipoprotein cholesterol (p <0.001). Thus, our findings suggest that treatment with rosuvastatin in patients with hypercholesterolemia may lead to a significant reduction in plasma ADMA levels, which appear to be related to the improvement in endothelial function by rosuvastatin.
Thalidomide with peginterferon alfa-2b and ribavirin in the treatment of non-responders genotype 1 chronic hepatitis C patients: proof of concept.

fewer than half of patients infected with hepatitis C virus (HCV) achieve sustained viral clearance after peginterferon alfa/ribavirin (Peg-IFN/RBV) therapy.



thalidomide posses anti-inflammatory and immunomodulatory properties through inhibition of tumor necrosis factor and costimulatory effect on human CD8+ T cells.



we started a prospective, open label trial of retreatment of very-difficult-to-treat genotype 1 chronic hepatitis C patients (CHC) patients, who had failed to respond to the (Peg-IFN/RBV), with a triple therapy consisting in these same antivirals plus thalidomide 200 mg/day (the TRITAL study).



none of the eleven patients fulfilling the inclusion criteria and included in the trial reached complete early virological response or sustained virological response. Viral load decline after 12 weeks of triple therapy thalidomide-based retreatment did not differ from viral dynamics during the first course. The triple therapy was well tolerated and only one patient developed mild bilateral neuropathy.



thalidomide addition to standard therapy is tolerated and did not increase the SVR rate in very-difficult-to-treat genotype 1 CHC patients. Different schedules are warranted to improve attempting retreatment of non responder CHC patients.
Evaluation of 17-mm St. Jude Medical Regent prosthetic aortic heart valves by rest and dobutamine stress echocardiography

The prosthesis used for aortic valve replacement in patients with small aortic root can be too small in relation to body size, thus showing high transvalvular gradients at rest and/or under stress conditions. This study was carried out to evaluate rest and Dobutamine stress echocardiography (DSE) hemodynamic response of 17-mm St. Jude Medical Regent (SJMR-17 mm) in relatively aged patients at mean 24 months follow-up.



The study population consisted of 19 patients (2 men, 17 women, mean age 69.2 +/- 7.3 years). All patients underwent rest Doppler echocardiography before and after surgery and basal and DSE at follow up (infused at rate of 5 microg/Kg/min and increased by 5 microg/Kg/min at 5 min intervals up to 40 microg/Kg/min). The following parameters were evaluated at rest and/or under DSE: heart rate (HR), ejection fraction (EF), cardiac output (CO), peak and mean velocity and pressure gradients (MxV, MnV, MxPG, MnPG), effective orifice area (EOA), indexed EOA (EOAi), left ventricular mass (LVM), indexed LVM (LVMi), Velocity Time Integral at left ventricular outflow tract (VTI LVOT) and transvalvular (Aortic VTI), Doppler velocity index (DVI). At rest MxPG and MnPG were 29.2 +/- 7.1 and 16.6 +/- 5.8 mmHg, respectively; EOA and EOAi resulted 1.14 +/- 0.3 cm(2) and 0.76 +/- 0.2 cm(2)/m(2); DVI was normal (0.50 +/- 0.1). At follow-up LVM and LVMi decreased significantly from pre-operative value of 258 +/- 43 g and 157.4 +/- 27.7 g/m(2) to 191 +/- 23.8 g and 114.5 +/- 10.6 g/m(2), respectively. DSE increased significantly HR, CO, EF, MxGP (up to 83.4 +/- 2 1.9 mmHg), MnPG (up to 43.2 +/- 12.7 mmHg). EOA, EOAi, DVI increased insignificantly (from baseline up to 1.2 +/- 0.4 cm(2), 0.75 +/- 0.3 cm(2)/m(2) and 0.48 +/- 0.1 respectively). Two patients developed significant intraventricular gradients.



These data show that SJMR 17-mm prostheses can be safely implanted in aortic position in relatively aged patients, offering a satisfactory hemodynamic performance at rest and under DSE, with full utilization of its available orifice, suggesting that a possible mild prosthesis-patient mismatch is not an issue of clinical relevance when this small prosthesis is used. Rest and Dobutamine stress echocardiography is a useful and effective means for evaluating prosthesis hemodynamics and for monitoring the expected LVH regression.
Cell therapy, a new standard in management of chronic critical limb ischemia and foot ulcer.

Fifty percent of diabetics (7% of general population) suffer from peripheral arterial occlusive disease, which may lead to amputation due to critical limb ischemia (CLI). The aim of our study was to prevent major limb amputation (MLA) in this group of patients using a local application of autologous bone marrow stem cells (ABMSC) concentrate. A total of 96 patients with CLI and foot ulcer (FU) were randomized into groups I and II. Patients in group I (n = 42, 36 males, 6 females, 66.2 ± 10.6 years) underwent local treatment with ABMSC while those in group II (n = 54, control, 42 males, 12 females, 64.1 ± 8.6 years) received standard medical care. The frequency of major limb amputation in groups I and II was 21% and 44% within the 120 days of follow up, respectively (p < 0.05). Only in salvaged limbs of group I both toe pressure and toe brachial index increased (from 22.66 ± 5.32 to 25.63 ± 4.75 mmHg and from 0.14 ± 0.03 to 0.17 ± 0.03, respectively, mean ± SEM). The CD34(+) cell counts in bone marrow concentrate (BMC) decreased (correlation, p = 0.024) with age, even though there was no correlation between age and healing. An unexpected finding was made of relative, bone marrow lymphopenia in the initial bone marrow concentrates in patients who failed ABMSC therapy (21% of MLA). This difference was statistically significant (p < 0.040). We conclude ABMSC therapy results in 79% limb salvage in patients suffering from CLI and FU. In the remaining 21% lymphopenia and thrombocytopenia were identified as potential causative factors, suggesting that at least a partial correction with platelet supplementation may be beneficial.
Branched-chain amino acids reduce hepatic iron accumulation and oxidative stress in hepatitis C virus polyprotein-expressing mice

Branched-chain amino acids (BCAA) reduce the incidence of hepatocellular carcinoma (HCC) in patients with cirrhosis. However, the mechanisms that underlie these effects remain unknown. Previously, we reported that oxidative stress in male transgenic mice that expressed hepatitis C virus polyprotein (HCVTgM) caused hepatic iron accumulation by reducing hepcidin transcription, thereby leading to HCC development. This study investigated whether long-term treatment with BCAA reduced hepatic iron accumulation and oxidative stress in iron-overloaded HCVTgM and in patients with HCV-related advanced fibrosis.



Male HCVTgM were fed an excess-iron diet that comprised either casein or 3.0% BCAA, or a control diet, for 6 months.



For HCVTgM, BCAA supplementation increased the serum hepcidin-25 levels and antioxidant status [ratio of biological antioxidant potential (BAP) relative to derivatives of reactive oxygen metabolites (dROM)], decreased the hepatic iron contents, attenuated reactive oxygen species generation, and restored mitochondrial superoxide dismutase expression and mitochondrial complex I activity in the liver compared with mice fed the control diet. After 48 weeks of BCAA supplementation in patients with HCV-related advanced fibrosis, BAP/dROM and serum hepcidin-25 increased and serum ferritin decreased compared with the pretreatment levels.



BCAA supplementation reduced oxidative stress by restoring mitochondrial function and improved iron metabolism by increasing hepcidin-25 in both iron-overloaded HCVTgM and patients with HCV-related advanced fibrosis. These activities of BCAA may partially account for their inhibitory effects on HCC development in cirrhosis patients.
Baseline serum cholestanol as predictor of recurrent coronary events in subgroup of Scandinavian simvastatin survival study. Finnish 4S Investigators.

To investigate whether baseline serum cholestanol:cholesterol ratio, which is negatively related to cholesterol synthesis, could predict reduction of coronary events in the Scandinavian simvastatin survival study.  Follow up of patients with coronary heart disease in whom baseline ratios were related to major coronary events.  Four universities in Finland.  A subgroup of 868 patients with coronary heart disease selected from the Scandinavian simvastatin survival study.  Treatment with simvastatin or placebo.  Serum concentrations of low density lipoprotein and high density lipoprotein cholesterol, total triglyceride concentration, and cholesterol:cholestanol ratio. Major coronary events.  With increasing baseline quarter of cholestanol distribution the reduction in relative risk increased gradually from 0.623 (95% confidence interval 0.395 to 0.982) to 1.166 (0.791 to 1.72). The risk of recurrence of major coronary events increased 2.2-fold (P < 0.01) by multiple logistic regression analysis between the lowest and highest quarter of cholestanol. The ratio of cholestanol was related inversely to the body mass index and directly to high density lipoprotein cholesterol and triglyceride concentrations but their quarters of distribution were not related to risk reduction.  Measurement of serum cholestanol concentration revealed a subgroup of patients with coronary heart disease in whom coronary events were not reduced by simvastatin treatment. Thus, patients with high baseline synthesis of cholesterol seem to be responders whereas those with low synthesis of cholesterol are non-responders.
Case finding for chronic obstructive pulmonary disease in primary care: a pilot randomised controlled trial.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. However, much of the disease burden remains undiagnosed.



To compare the yield and cost effectiveness of two COPD case-finding approaches in primary care.



Pilot randomised controlled trial in two general practices in the West Midlands, UK.



A total of 1634 ever-smokers aged 35-79 years with no history of COPD or asthma were randomised into either a 'targeted' or 'opportunistic' case-finding arm. Respiratory questionnaires were posted to patients in the 'targeted' arm and provided to patients in the 'opportunistic' arm at routine GP appointments. Those reporting at least one chronic respiratory symptom were invited for spirometry. COPD was defined as pre-bronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC)<0.7 and FEV1<80% of predicted. Primary outcomes were the difference in the proportion of patients diagnosed with COPD and the cost per case detected.



Twenty-six per cent (212/815) in the 'targeted' and 13.6% (111/819) in the 'opportunistic' arm responded to the questionnaire and 78.3% (166/212) and 73.0% (81/111), respectively, reported symptoms; 1.2% (10/815) and 0.7% (6/819) of patients in the 'targeted' and 'opportunistic' arms were diagnosed with COPD (difference in proportions = 0.5% [95% confidence interval {CI} = -0.5% to 3.08%]). Over a 12-month period, the 'opportunistic' case-finding yield could be improved to 1.95% (95% CI = 1.0% to 2.9%). The cost-per case detected was £424.56 in the 'targeted' and £242.20 in the 'opportunistic' arm.



Opportunistic case finding may be more effective and cost effective than targeting patients with a postal questionnaire alone. A larger randomised controlled trial with adequate sample size is required to test this.
Measurement of Moisture in Wood for Application in the Restoration of Old Buildings

There are many historic buildings whose construction is based on timber frame walls. Most buildings built during the nineteenth and early twentieth centuries were based on timber frame walls with vertical support elements. These timber frame elements are affected by their moisture content and by the passage of time. If the interaction of the timber frame walls with hygrothermal fluctuations were known, the maintenance of these buildings could be improved significantly. To determine the moisture content of wood there are two types of meters on the market: on the one hand, capacitance meters which consist of two side ends and where the moisture content is measured locally between two peaks. On the other hand, there are meters based on the variation of electromagnetic transmittance of timber, which depends on the moisture of timber. The second ones are very expensive and difficult to handle. This work presents a new non-intrusive capacitive sensor that measures the global moisture content in a section of the timber frame walls and therefore its accuracy is similar to the accuracy that can be obtained with electromagnetic transmittance meters. Additionally, as it is a capacitive sensor, it is low cost and easy to operate.