nils-herrmann/clean_scirepeval huggingface dataset:
Gentamicin-induced correction of CFTR function in patients with cystic fibrosis and CFTR stop mutations.

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene containing a premature termination signal cause a deficiency or absence of functional chloride-channel activity. Aminoglycoside antibiotics can suppress premature termination codons, thus permitting translation to continue to the normal end of the transcript. We assessed whether topical administration of gentamicin to the nasal epithelium of patients with cystic fibrosis could result in the expression of functional CFTR channels.



In a double-blind, placebo-controlled, crossover trial, patients with stop mutations in CFTR or patients homozygous for the DeltaF508 mutation received two drops containing gentamicin (0.3 percent, or 3 mg per milliliter) or placebo in each nostril three times daily for two consecutive periods of 14 days. Nasal potential difference was measured at base line and after each treatment period. Nasal epithelial cells were obtained before and after gentamicin treatment from patients carrying stop mutations, and the C-terminal of surface CFTR was stained.



Gentamicin treatment caused a significant reduction in basal potential difference in the 19 patients carrying stop mutations (from -45+/-8 to -34+/-11 mV, P=0.005) and a significant response to chloride-free isoproterenol solution (from 0+/-3.6 to -5+/-2.7 mV, P<0.001). This effect of gentamicin on nasal potential difference occurred both in patients who were homozygous for stop mutations and in those who were heterozygous, but not in patients who were homozygous for DeltaF508. After gentamicin treatment, a significant increase in peripheral and surface staining for CFTR was observed in the nasal epithelial cells of patients carrying stop mutations.



In patients with cystic fibrosis who have premature stop codons, gentamicin can cause translational "read through," resulting in the expression of full-length CFTR protein at the apical cell membrane, and thus can correct the typical electrophysiological abnormalities caused by CFTR dysfunction.
Efficacy of cranial electric stimulation for the treatment of insomnia: a randomized pilot study.

This pilot study examined the potential efficacy of cranial electric stimulation for the treatment of insomnia.



The researchers tested the hypothesis through a randomized, double-blind, and placebo controlled clinical trial. The researchers approached eligible subjects who scored 21 or above on the Pittsburgh Insomnia Rating Scale. The researchers then randomly assigned the subjects to receive either an active or sham device. Each study subject received 60min of active or sham treatment for five days. Following each intervention the subjects completed a sleep log, as well as three and ten days later.



The researchers conducted the study among active duty service members receiving mental health care on the Psychiatry Continuity Service (PCS), Walter Reed National Military Medical Center in Bethesda, MD.



The study's primary outcome variables were the time to sleep onset, total time slept, and number of awakenings as reported by the subjects in the serial sleep logs. The researchers identified a nearly significant increase in total time slept after three cranial electric stimulation treatments among all study subjects. A closer examination of this group revealed an interesting gender bias, with men reporting a robust increase in total time slept after one treatment, decay in effect over the next two interventions, and then an increase in total time slept after the fourth treatment. The researchers speculate that the up and down effect on total time slept could be the result of an insufficient dose of cranial electric stimulation.
Effect of unfractionated and low-molecular-weight heparin on OPG, sRANKL, and von Willebrand factor concentrations during hemodialysis.

Endothelial dysfunction marker, von Willebrand factor (vWF), is physically connected with osteoprotegerin (OPG) in the Weibel-Palade bodies. We aimed to compare the effect of unfractionated (UFH) and low-molecular-weight (LMWH enoxaparin) heparin used as anticoagulants during hemodialysis (HD) on plasma levels and relationships of OPG, soluble receptor activator of nuclear factor κB Ligand (sRANKL), and vWF.



Totally 21 clinically stable chronic HD patients were randomly assigned to either enoxaparin (n = 10) or UFH (n = 11) anticoagulation and followed prospectively for 12 weeks before crossing over to the alternate therapy for further 12 weeks. The OPG, RANKL, and vWF levels were measured at T0, T10, and T180 of HD session after each period of evaluation.



The baseline sRANKL level was higher under UFH treatment. Its over-HD level does not behave significantly different under enoxaparin and UFH treatment. Plasma OPG levels expressly changed during both enoxaparin (χ(2) analysis of variance [ANOVA] = 31.13, P < .016) and UFH (χ(2) ANOVA = 8.26, P = .016) anticoagulation, and its increment at T10 and T180 was significantly different between both the heparins. The main negative predictor of OPG concentration was the total cholesterol level (β = -.51, P = .025). von Willebrand factor concentration remained stable during UFH anticoagulation, whereas constant, no significant increments were noticed, under enoxaparin treatment. After 10 minutes of HD, especially under enoxaparin use, a positive correlation between OPG and vWF increase was noticed (P = .03, R = .45).



Impact of heparin on endothelial cells and simultaneously on OPG/RANK/RANKL axis reinforces the presumption of the pathophysiological linkage between bone mineralization and endothelial dysfunction in end-stage renal disease.
The Inhaled Steroid Treatment As Regular Therapy in Early Asthma (START) study 5-year follow-up: effectiveness of early intervention with budesonide in mild persistent asthma.

The Inhaled Steroid Treatment as Regular Therapy in Early Asthma (START) study enrolled 7241 patients aged 5 to 66 years with recent-onset, mild persistent asthma to assess early intervention with the inhaled corticosteroid budesonide on long-term asthma control.



The open-label phase of the START study was included to determine the effect on lung function and asthma control of adding budesonide to the reference group patients who had not initially received inhaled corticosteroids.



Patients were randomized to double-blind treatment with budesonide, 200 mug (those aged < 11 years) or 400 mug once daily, or placebo plus the usual asthma therapy for 3 years, after which all patients received 2 years of open-label treatment with budesonide once daily.



During the full 5-year study period, postbronchodilator FEV(1) percent predicted decreased, irrespective of randomized treatment during the double-blind phase, by an average of 2.22% (SE, 0.15%). However, patients with inhaled budesonide in the double-blind phase had a significantly lower risk (odds ratio, 0.61; P < .001) of a severe asthma-related event during the full 5-year study period than those in the reference group. Moreover, patients in the reference group used more additional asthma medications during both the open-label and double-blind phases.



In mild persistent asthma early intervention with inhaled budesonide was associated with improved asthma control and less additional asthma medication use.
Rationale and design of the Pan Australasian chemotherapy-induced emesis burden of illness study

Preventing and managing chemotherapy-induced nausea and vomiting (CINV) remain important goals. The objective of the Pan Australasian chemotherapy-induced emesis burden of illness (PrACTICE) study was to describe the incidence of CINV after highly or moderately emetogenic chemotherapy (HEC or MEC) for cancer in current clinical practice in Australia and five Asian countries (China, India, Singapore, South Korea, and Taiwan). This prospective, observational study of CINV was conducted at 31 sites in these six countries from August 2011 through September 2012 and enrolled male and female adult patients (≥18 years of age) naïve to HEC and MEC who were scheduled to receive at least two cycles of single-day chemotherapy. The primary effectiveness endpoint was complete response, defined as no vomiting or use of rescue therapy, during chemotherapy cycle 1 in the overall phase (0–120 h), acute phase (0–24 h), and delayed phase (>24–120 h). Study outcomes were analyzed descriptively. Primary outcomes, CINV incidence, and treatment patterns (chemotherapy, CINV prophylaxis, rescue medication prescription, and rescue medication use) were assessed by phase (overall, acute, delayed), by cycle (as appropriate), within and across countries, and by level of chemotherapy emetogenicity (HEC vs MEC). The impact of CINV in cycle 1 on CINV in cycle 2 was analyzed for all patients with evaluable data for cycle 2. No site-specific analyses were performed. The remainder of this special series of papers reports on the results of this study.
Osteocel Plus cellular allograft in anterior cervical discectomy and fusion: evaluation of clinical and radiographic outcomes from a prospective multicenter study.

Prospective, multicenter, nonrandomized, institutional review board-approved clinical and radiographic study.



To evaluate and summarize the 2-year outcomes of patients treated with Osteocel Plus cellular allograft as part of an anterior cervical discectomy and fusion procedure.



Osteocel Plus is an allograft cellular bone matrix containing native mesenchymal stem cells and osteoprogenitor cells that is intended to mimic the performance of iliac crest autograft without the morbidity associated with its harvest.



A total of 182 patients were treated with anterior cervical discectomy and fusion using Osteocel Plus in a polyetheretherketone cage and anterior plating at 1 or 2 consecutive levels. Clinical outcomes included visual analogue scale for neck and arm pain, neck disability index, and SF-12 physical and mental component scores. Computed tomography and plain film radiographic measures included assessment of bridging bone, disc height, disc angle, and segmental range of motion.



A total of 249 levels were treated in 182 patients. Mean procedure time was 100 minutes, blood loss was less than 50 mL in 93% of patients, and hospital stay was 1 day or less in 84% of patients. Significant (P<0.05) average improvements in clinical outcomes from preoperatively to 24 months included the following: neck disability index: 21.5%; visual analogue scale neck: 34 mm; visual analogue scale arm: 35 mm; SF-12 physical component score: 11.2; SF-12 mental component score: 6.8. At 24 months, 93% of patients were satisfied with their outcome. In patients treated at a single level with a minimum of 24-month follow-up, 92% (79/86) of levels achieved solid bridging and 95% of levels demonstrated range of motion of less than 3°. In combined single- and 2-level procedures, 87% (157/180) of levels achieved solid bridging and 92% (148/161) had range of motion of less than 3° at 24 months. No patient required revision for pseudarthrosis.



Improvements in clinical results at 2 years, high patient satisfaction, and high radiographic and clinical fusion rates provide confidence in Osteocel Plus as an effective alternative to structural allograft or autograft in anterior cervical discectomy and fusion procedures.
Radiotherapy with concurrent carbogen and nicotinamide in bladder carcinoma.

Phase II clinical studies suggest that hypoxic modification with carbogen and nicotinamide (CON) may increase the efficacy of radiotherapy (RT).



Three hundred thirty-three patients with locally advanced bladder carcinoma were randomly assigned to RT alone versus RT with CON. A schedule of either 55 Gy in 20 fractions in 4 weeks or 64 Gy in 32 fractions in 6.5 weeks was used. The primary end point was cystoscopic control at 6 months (CC(6m)) and secondary end points were overall survival (OS), local relapse-free survival (RFS), urinary and rectal morbidity.



CC(6m) was 81% for RT + CON and 76% for RT alone (P = .3); however, just more than half of patients underwent cystoscopy at that time. Three-year estimates of OS were 59% and 46% (P = .04) and 3-year estimates of RFS were 54% and 43% (P = .06) for RT + CON versus RT alone. Risk of death was 14% lower with RT + CON (P = .04). In multivariate comparison, RT + CON significantly reduced the risk of relapse (P = .05) and death (P = .03). There was no evidence that differences in late urinary or GI morbidity between treatment groups or between fractionation schedules were significant.



RT + CON produced a small nonsignificant improvement in CC(6m). Differences in OS, risk of death, and local relapse were significantly in favor of RT + CON. Late morbidity was similar in both trial arms. Results indicate a benefit of adding CON to radical RT.
Waist circumference is the key risk factor for diabetes in Korean women with history of gestational diabetes.

This study investigated relationships between various obesity indices and an onset of type 2 diabetes mellitus (TY2DM) in Korean women with history of gestational diabetes mellitus (GDM). A total of 909 women with history of GDM were enrolled from the four major hospitals, and the first postpartum follow-up examination was made at 6 weeks, and annually thereafter. During postpartum follow-up period, mean 2.13+/-1.75 years, we conducted 2h 75 g OGTT and measured glucose, insulin, c-peptide, lipid profiles, lifestyle and dietary evaluation. For obesity parameters, we measured body weight, body mass index (BMI), waist and hip circumference, subcutaneous fat thickness, body fat percent and weight using bioelectrical impedance tests. Diabetes incidence for 6 years was 12.8% and all the obesity indices were significantly higher in subjects with diabetes or glucose intolerance than those with normal glucose tolerance (p<0.001). When obesity indices were compared between <25th versus >75th percentile, the waist circumference presented with the strongest relationship (odds ratio=5.8, 95% CI 2.8-11.8). This relationship persisted, OR=3.86 (95% CI 1.8-8.2), even after adjusting for the potential confounders. This prospective study revealed that waist circumference is one of the key risk factors for the onset of diabetes in Korean women with history of GDM.
Gold levels produced by treatment with auranofin and sodium aurothiomalate.

Sixty-three patients with rheumatoid arthritis were randomly divided into 3 groups, and treated with either sodium aurothiomalate (Myocrisin), auranofin, or placebo. Gold levels in whole blood, plasma, and haemolysate were measured serially along with clinical and laboratory parameters of efficacy. Auranofin produced a higher ratio of haemolysate to plasma gold than Myocrisin, and it appears that the affinity of the red cell for gold is reduced during therapy with auranofin. Gold levels did not correlate with changes in the pain score, erythrocyte sedimentation rate, and C-reactive protein, nor with the development of toxicity. In the Myocrisin group the haemolysate gold level achieved was dependent on the number of cigarettes smoked. In the auranofin group there was no such correlation, but the haemolysate gold level was higher for smokers than non-smokers. The likely action of gold is discussed.
Correlation between eight-gene expression profiling and response to therapy of newly diagnosed multiple myeloma patients treated with thalidomide–dexamethasone incorporated into double autologous transplantation

We performed a molecular study aimed at identifying a gene expression profile (GEP) signature predictive of attainment of at least near complete response (CR) to thalidomide–dexamethasone (TD) as induction regimen in preparation for double autologous stem cell transplantation in 112 younger patients with newly diagnosed multiple myeloma. A GEP supervised analysis was performed on a training set of 32 patients, allowing to identify 157 probe sets differentially expressed in patients with CR versus those failing CR to TD. We then generated an eight-gene GEP signature whose performance was subsequently validated in a training set of 80 patients. A correct prediction of response to TD was found in 71 % of the cases analyzed. The eight genes were downregulated in patients who achieved CR to TD. Comparisons between post-autotransplantation outcomes of the 44 non-CR-predicted patients and of the 36 CR-predicted patients showed that this latter subgroup had a statistically significant benefit in terms of higher rate of CR after autotransplant(s) and longer time to progression, event-free survival, and overall survival. These results can be an important first step to identify at diagnosis those patients who will respond more favourably to a particular treatment strategy.
A Randomized Controlled Study on the Effects of Bisoprolol and Atenolol on Sympathetic Nervous Activity and Central Aortic Pressure in Patients with Essential Hypertension

β-blockers (BBs) with different pharmacological properties may have heterogeneous effects on sympathetic nervous activity (SNA) and central aortic pressure (CAP), which are independent cardiovascular factors for hypertension. Hence, we analyzed the effects of bisoprolol and atenolol on SNA and CAP in hypertensive patients.



This was a prospective, randomized, controlled study in 109 never-treated hypertensive subjects randomized to bisoprolol (5 mg) or atenolol (50 mg) for 4-8 weeks. SNA, baroreflex sensitivity (BRS) and heart rate (HR) variability (HRV) were measured using power spectral analysis using a Finometer. CAP and related parameters were determined using the SphygmoCor device (pulse wave analysis).



Both drugs were similarly effective in reducing brachial BP. However, central systolic BP (-14±10 mm Hg vs -6±9 mm Hg; P<0.001) and aortic pulse pressure (-3±10 mm Hg vs +3±8 mm Hg; P<0.001) decreased more significantly with bisoprolol than with atenolol. The augmentation index at a HR of 75 bpm (AIxatHR75) was significantly decreased (29%±11% to 25%±12%; P = 0.026) in the bisoprolol group only. Furthermore, the change in BRS in the bisoprolol group (3.99±4.19 ms/mmHg) was higher than in the atenolol group (2.66±3.78 ms/mmHg), although not statistically significant (P>0.05). BRS was stable when RHR was controlled (RHR≤65 bpm), and the two treatments had similar effects on the low frequency/high frequency (HF) ratio and on HF.



BBs seem to have different effects on arterial distensibility and compliance in hypertensive subjects. Compared with atenolol, bisoprolol may have a better effect on CAP.
Naltrexone vs. Nefazodone for Treatment of Alcohol Dependence: A Placebo-Controlled Trial

This study compared the effects of nefazodone, a serotonergic antidepressant, with the opioid antagonist naltrexone, and an inactive placebo in 183 alcohol-dependent subjects receiving weekly relapse prevention psychotherapy. Following a single-blind, placebo lead-in period, subjects were randomly assigned to receive study medication, which they took under double-blind conditions for 11 weeks. Naltrexone treatment was associated with significantly more adverse neuropsychiatric and gastrointestinal effects, poorer compliance, and a greater rate of treatment attrition. There were no reliable between-group differences in drinking behavior. These results indicate that nefazodone is not efficacious for treatment of alcohol dependence. Furthermore, the clinical utility of naltrexone seems to be limited by its adverse effects, a finding that has important implications for efforts to develop medications to treat alcohol dependence.
Low-dose of thalidomide in the treatment of refractory myeloma.

history of granulomatosis, hepatosplenomegaly, HBsAg and EBV-VCA positivity. The only surviving patient had received an allogeneic bone-marrow transplantation. Our two children had been infected by EBV with a chronic high titer of IgG against EBV-VCA, consistent with a life-long infection.9 EBV may infect T-cells creating reactive lymphoid proliferations without contributing to the neoplastic process; however EBV or other viral infections (i.e. Cytomegalovirus, hepatitis B), or immune defects suppressing NK activity – such as altered T4/T8 ratio – may lead to neoplastic transformation in particular hosts, and this could be the case with our patients. All available lymph node samples were therefore submitted to EBV-DNA detection without finding amplification of the viral genome. The presence of EBV-DNA is a feature of angioimmunoblastic PTCL found in Eastern Countries, being less common in Europe.3,10 As to optimal treatment, we agree with the Taiwan group:3 marrow transplantation can cure this disease. The role of retinoic acid cannot be assessed by anecdotal experiences, even though malignant cell differentiation and apoptosis might depend on retinoic acid administration.10 No national or international co-operative group is currently dealing with poor-prognosis PTCL: a common study is therefore needed, perhaps including both adults and children.
Way-tagged cache: an energy-efficient L2 cache architecture under write-through policy

Write-through policy employed in many high-performance microprocessors provides good tolerance to soft errors in cache systems. However, it also incurs large energy overhead due to the increased accesses to caches at the lower level (e.g., the L2 cache) during write operations. In this paper, we propose a new cache architecture referred to as way-tagged cache to improve the energy efficiency of write-through cache systems. By maintaining the way tags of the L2 cache in the L1 cache during read operations, the proposed technique enables the L2 cache to work in an equivalent direct-mapping manner during write hits, which account for the majority of L2 cache accesses. This leads to significant energy reduction. Simulation results on the SPEC CPU2000 benchmarks demonstrate that the proposed technique achieves 65.4% energy savings on average with about 0.02% area overhead and no performance degradation.
A Randomized , Double-Blind Trial Comparing Pegylated Interferon Alfa-2 b to Interferon Alfa-2 b as Initial Treatment for Chronic Hepatitis C

This international, randomized, active-controlled, parallel-group, double-blind dose-finding study compared peginterferon alfa-2b (PegIntronTM) to interferon alfa-2b for the initial treatment of compensated chronic hepatitis C. We randomly assigned 1,219 subjects to receive either the standard three-times-weekly (TIW) interferon alfa-2b dose (3 MIU) or the once-weekly (QW) peginterferon alfa-2b (0.5, 1.0, or 1.5 g/kg). Subjects were treated for 48 weeks and then followed for an additional 24 weeks. All 3 peginterferon alfa-2b doses significantly (P < .042) improved virologic response rates (loss of detectable serum HCV RNA) after treatment and after follow-up, as compared with interferon alfa-2b. Unlike the end-of-treatment virologic response, the sustained virologic response rate was not doserelated above 1.0 g/kg peginterferon alfa-2b because of a higher relapse rate among patients treated with 1.5 g/kg peginterferon alfa-2b, particularly among patients infected with genotype 1. All 3 peginterferon alfa-2b doses decreased liver inflammation to a greater extent than did interferon alfa-2b, particularly in subjects with sustained responses. No new adverse events were reported, and the majority of adverse events and changes in laboratory values were mild or moderate. In conclusion, peginterferon alfa-2b maintained (0.5 g/kg) or surpassed (1.0, 1.5 g/kg) the clinical efficacy of interferon alfa-2b while preserving its safety profile. The higher rate of virologic response during treatment with 1.5 g/kg peginterferon alfa-2b in patients infected with genotype 1 and high viral levels warrants further evaluation. (HEPATOLOGY 2001;34:395-403.