nils-herrmann/clean_scirepeval huggingface dataset:
Phase II study of imatinib mesylate and hydroxyurea for recurrent grade III malignant gliomas

Recent reports demonstrate the activity of imatinib mesylate, an ATP-mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme. We performed the current phase 2 study to evaluate this regimen among patients with recurrent WHO grade III malignant glioma (MG). Patients with grade III MG at any recurrence, received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme inducing anti-epileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Clinical assessments were performed monthly and radiographic assessments were obtained at least every 2 months. The primary endpoint was 6-month progression-free survival (PFS) rate. Thirty-nine patients were enrolled. All patients had progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. The median number of episodes of prior progression was 2 (range, 1–7) and the median number of prior treatment regimens was 3 (range, 1–8). With a median follow-up of 82.9 weeks, 24% of patients were progression-free at 6 months. The radiographic response rate was 10%, while 33% achieved stable disease. Among patients who achieved at least stable disease at first evaluation, the 6-month and 12-month PFS rates were 53% and 29%, respectively. The most common grade 3 or greater toxicities were hematologic and complicated less than 4% of administered courses. Imatinib mesylate plus hydroxyurea, is well tolerated and associated with anti-tumor activity in some patients with recurrent grade 3 MG.
Intra-individual head-to-head comparison of Sirolimus®- and Paclitaxel®-eluting stents for coronary revascularization. A randomized, multi-center trial.

Despite the known effects of drug-eluting stents (DES), other cofactors attributed to patient characteristics affect their success. Interest focused on designing a study minimizing these factors to answer continuing concerns on the heterogeneity of response to different DESs. The study's aim was to investigate the feasibility and impact of an intra-individual comparison design in patients (pts) with two coronary artery stenosis treated with a Sirolimus- (SES) and a Paclitaxel- (PES) eluting stent.



The study was conducted as a prospective, randomized, multi-center trial in 112 pts who consented to treatment with a SES and a PES. Pts were eligible if they suffered from the presence of two single primary target lesions in two different native coronary arteries. Lesions were randomized to either SES or PES treatment. The primary endpoint was in-stent luminal late loss (LLL), as determined by quantitative angiography at 8 months; clinical follow up was obtained at 1, 8, and 12 months additionally. The LLL (0.13 ± 0.28 mm SES vs. 0.26 ± 0.35 mm PES, p=0.011) showed less neointima in SES. With a predefined cut-off criterion of 0.2mm difference in LLL, 53/87 pts SES and PES were similar effective. 34/87 pts had a divergent result, 26 pts had greater benefit from SES while 8 pts had greater benefit from PES. Overall, MACE (MI, TLR, and death) occurred in 19 (17%) pts. Based on lesion analysis of 108 lesions treated with SES and 110 lesions treated with PES, 5 (4.6%) lesions with SES and 3 (2.7%) lesions with PES required repeated TLR.



An intra-individual comparison design to assess differences in efficacy of different DESs is feasible, safe and achieves similar results to inter-individual studies. This study is among the first to show that failure of one DES does not necessarily implicate failure of another DES and vice versa.
Molecular detection of minimal residual disease in adult and childhood acute lymphoblastic leukaemia reveals differences in treatment response

Immunoglobulin heavy chain gene (IgH gene) rearrangements are found in the majority of patients with B lineage acute lymphoblastic leukaemia (ALL). Two hundred and three bone marrow samples from 54 patients (33 adults and 21 children) were analysed by PCR within specific time-points after diagnosis (ie 1, 2–3, 4–6 and 7–12 months) using FR1 and JH primers (fingerprinting with a sensitivity ⩾1:5 × 103). CDR3-derived allele specific oligoprimers (ASO to achieve a sensitivity between 1:104 and 1:105) were applied to 12 children and 18 adults, while size of CDR3 region, oligoclonality and background problems prevented their application to the remaining patients. All patients were followed clinically for ⩾24 months. Thirty adults and 16 children presented as newly diagnosed ALL, while the remaining eight patients were analysed in first or subsequent relapse. Patients destined to relapse showed a higher proportion of positive tests (⩾50%), particularly after 1 month, than in the remission group, irrespective of age. Among patients staying in remission, a decrease in MRD-positive tests occurred during the first 12 months in both age groups. However, the proportion of positive tests dropped below 15% at a later stage in adults (4–6 months) than in children (2–3 months). Among children, only patients destined to relapse were MRD positive beyond 1 month, with the exception of only one patient, still positive at 2–3 months in the remission group. The difference in MRD positivity between relapse and remission patients was statistically significant in children (P < 0.03) at any time of testing, but only at 4–6 months in adults (P < 0.01). these data suggest that resolution of mrd in all occurs more rapidly in children compared to adults, particularly within the first 6 months. children and adults, studied in first or subsequent relapse, showed a higher proportion of positive tests during reinduction compared to newly diagnosed patients.
Proportional assist ventilation as an aid to exercise training in severe chronic obstructive pulmonary disease.

The effects of providing ventilatory assistance to patients with severe chronic obstructive pulmonary disease (COPD) during a high intensity outpatient cycle exercise programme were examined.



Nineteen patients (17 men) with severe COPD (mean (SD) forced expiratory volume in 1 second (FEV(1)) 27 (7)% predicted) underwent a 6 week supervised outpatient cycle exercise programme. Ten patients were randomised to exercise with ventilatory assistance using proportional assist ventilation (PAV) and nine (two women) to exercise unaided. Before and after training patients performed a maximal symptom limited incremental cycle test to determine peak work rate (Wpeak) followed by a constant work rate (CWR) test at 70% of Wpeak achieved in the baseline incremental test. Minute ventilation (VE), heart rate, and arterialised venous plasma lactate concentration [La(+)] were measured before and after each test.



Mean training intensity (Wt/Wpeak) at 6 weeks was 15.2% (95% CI 3.2 to 27.1) higher in the group that used ventilatory assistance (p=0.016). Peak work rate after training was 18.4% (95% CI 6.4 to 30.5) higher (p=0.005) in the assisted group (p=0.09). [La(+)] at an identical workload after training was reduced by 30% (95% CI 16 to 44) in the assisted group (p=0.002 compared with baseline) and by 11% (95% CI -7 to 31) (p=0.08 compared with baseline) in the unassisted group (mean difference 18.4% (95% CI 3.3 to 40), p=0.09). A significant inverse relationship was found between reduction in plasma lactate concentration (DeltaL) at an equivalent workload after training during the CWR test and Wt/Wpeak achieved during the last week of training (r=-0.7, p=0.0006).



PAV enables a higher intensity of training in patients with severe COPD, leading to greater improvements in maximum exercise capacity with evidence of true physiological adaptation.
Lowering effect on postprandial glycemic response of nopales added to Mexican breakfasts.

The burden of diabesity is increasing rapidly in Mexico (1). Culturally based diets with low glycemic index and glycemic load might be a low-cost approach for a population with a high index of socioeconomic marginality. Mixed meals are the usual manner of food intake, and they are different among regions of Mexico. Consumption of nopales (prickly pear cactus pads) in middle and low socioeconomic populations of central and southern Mexico is generally three times weekly. Nopales can be purchased at any food market in Mexico. The purpose of this study was to estimate the glycemic index of three usual Mexican breakfasts and to measure the effect of adding cactus pads (nopales) on postprandial glucose response in type 2 diabetic subjects.
Impact of smoking and smoking cessation on lung cancer mortality in the Asia-Pacific region.

Cigarette smoking is becoming increasingly common in Asia while quitting remains rare, in part because of a lack of knowledge about the risks of smoking. This study compared the risk of death from lung cancer associated with smoking habits in Australia and New Zealand and in Asia by using data from the Asia Pacific Cohort Studies Collaboration: 31 studies involving 480,125 individuals. Cox regression models were used. The hazard ratios for lung cancer mortality associated with current smoking were, for men, 2.48 (95% confidence interval (CI): 1.99, 3.11) in Asia versus 9.87 (95% CI: 6.04, 16.12) in Australia and New Zealand; p for homogeneity <0.0001. For women, the corresponding estimates were 2.35 (95% CI: 1.29, 4.28) in Asia versus 19.33 (95% CI: 10.0, 37.3) in Australia and New Zealand; p for homogeneity <0.0001. Quitting was beneficial in both regions; the hazard ratios for former compared with current smokers were 0.69 (95% CI: 0.53, 0.92) in Asia and 0.30 (95% CI: 0.22, 0.41) in Australia and New Zealand. The lesser effect in Asia was partly explained by the fewer number of cigarettes smoked and the shorter duration of follow-up in Asian studies. These results suggest that tobacco control policies in Asia should not solely concentrate on preventing the uptake of smoking but also attend to cessation.
Derivation and validation of a diagnostic model for the evaluation of left ventricular filling pressures and diastolic function using mitral annulus tissue Doppler imaging.

Several modalities to diagnose diastolic dysfunction by transthoracic echocardiography (TTE) exist. We compared the ratio of early mitral filling velocity (E) to early diastolic velocity by tissue Doppler imaging at the medial (E/E'm) and the lateral (E/E'l) mitral annulus and developed a model to diagnose elevated left ventricular end-diastolic pressure (LVEDP).



Sixty patients underwent same-day cardiac catheterization and TTE. Left ventricular end-diastolic pressure was recorded in addition to TTE data, including left atrial area (LAA), E/E'm, and E/E'l. An LVEDP >15 mm Hg was considered to be elevated and diagnostic of diastolic dysfunction.



E/E'm had a significantly higher correlation (r = 0.68, P < .001) than did E/E'l (r = 0.46, P < .001). By univariate analysis, LAA >18.75 cm(2), E/E'l >11.2, and E/E'm >15.75 were found to be significant predictors of high LV filling pressure. By multivariate binary logistic regression model analysis, only E/E'm and LAA were independent predictors of LVEDP >15 mm Hg. The presence of 1 variable had a sensitivity of 95% and a specificity of 43.4%, whereas the presence of 2 variables had a sensitivity of 76.2% and a specificity of 100%.



Use of a diagnostic model based on easily derived measurements such as E/E'm and LAA was a powerful noninvasive diagnostic modality for elevated LVEDP. Measurement of the mitral annulus velocity by tissue Doppler imaging at the medial aspect of the mitral valve appeared to be superior to that at the lateral aspect.
Neither dosage nor serum levels of antiepileptic drugs are predictive for efficacy and adverse effects

In order to assess whether doses or serum levels are predictive for the efficacy and adverse effects of antiepileptic drugs (AEDs), measures for exposure to drug combinations have to be used. For doses, the ratio of the observed prescribed daily dose (PDD) and the average defined daily dose (DDD) considered effective for the main indication of the drug was used. In analogy for serum levels, the OSL/ATL ratio,i.e. the ratio of the observed serum level and the average therapeutic level was used. In polypharmacy these ratios can be summed as they are normalized measures of strength. The correlations of these ratios with outcome measures were studied in 200 patients attending out-patient clinics of special centres for epilepsy; half of these patients were treated with monopharmacy and half with polypharmacy. As outcome measures the following indices were used: the index of seizures, which quantifies seizure type and frequency, the seizure activity index, the neurotoxicity score, the systemic toxicity score, and the composite index of impairments, which is the sum of the seizure activity index and the neurotoxicity score and the systemic toxicity score. When all data were pooled, the correlation coefficient between the PDD/DDD ratio and the OSL/ATL ratio was 0.77. However, when the data were examined separately for the monopharmacy and polypharmacy groups, the correlation was 0.31 for the monopharmacy group and 0.50 for the polypharmacy group. Neither the PDD/DDD ratio nor the OSL/ATL ratio correlated with the composite index of impairments or with any of the individual indices. Factors such as the difficulty of titrating the endpoint of seizure suppression and the development of tolerance to adverse drug effects may perhaps be responsible for these findings. This observational study signals the problem.
Impact of Energy Devices During Liver Parenchymal Transection: A Multicenter Randomized Controlled Trial

To clarify the benefit of energy devices such as ultrasonically activated device and bipolar vessel sealing device in liver surgeries. Several studies have suggested the benefit of energy devices in liver transection, while a randomized trial has found no association between their use and surgical outcomes. Patients scheduled to undergo open liver resection were eligible for this multicenter non-blinded randomized study. They were randomized to receive an energy device (experimental group) or not (control group) during liver transection. The primary endpoint was the proportion of patients with intraoperative blood loss >1,000 mL. The primary aim was to show non-inferiority of hepatectomy with energy device to that without energy device. A total of 212 patients were randomized and 211 (105 and 106 in the respective groups) were analyzed. Intraoperative blood loss >1,000 mL occurred in 15.0 % patients with energy device and 20.2 % patients without energy device. The experimental minus control group difference was −5.2 % (95 % confidence interval −13.8 to 3.3 %; non-inferiority test, p = 0.0248). Hepatectomy with energy device resulted in a shorter median liver transection time (63 vs. 84 min; p < 0.001) and a lower rate of postoperative bile leakage (4 vs. 16 %; p = 0.002). The hypothesis that hepatectomy with energy device is not inferior to that without energy device in terms of blood loss has been demonstrated. The use of energy devices during liver surgery is clinically meaningful as it shortens the liver transection time and reduces the incidence of postoperative bile leakage.
A prospective study of direct medical costs in a large cohort of consecutively enrolled patients with refractory epilepsy in Italy.

To evaluate direct medical costs and their predictors in patients with refractory epilepsy enrolled into the SOPHIE study (Study of Outcomes of PHarmacoresistance In Epilepsy) in Italy.



Adults and children with refractory epilepsy were enrolled consecutively at 11 tertiary referral centers and followed for 18 months. At entry, all subjects underwent a structured interview and a medical examination, and were asked to keep records of diagnostic examinations, laboratory tests, specialist consultations, treatments, hospital admissions, and day-hospital days during follow-up. Study visits included assessments every 6 months of seizure frequency, health-related quality of life (Quality of Life in Epilepsy Inventory 31), medication-related adverse events (Adverse Event Profile) and mood state (Beck Depression Inventory-II). Cost items were priced by applying Italian tariffs. Cost estimates were adjusted to 2013 values.



Of 1,124 enrolled individuals, 1,040 completed follow-up. Average annual cost per patient was € 4,677. The highest cost was for antiepileptic drug (AED) treatment (50%), followed by hospital admissions (29% of overall costs). AED polytherapy, seizure frequency during follow-up, grade III pharmacoresistance, medical and psychiatric comorbidities, and occurrence of status epilepticus during follow-up were identified as significant predictors of higher costs. Age between 6 and 11 years, and genetic (idiopathic) generalized epilepsies were associated with the lowest costs. Costs showed prominent variation across centers, largely due to differences in the clinical characteristics of cohorts enrolled at each center and the prescribing of second-generation AEDs. Individual outliers associated with high costs related to hospital admissions had a major influence on costs in many centers.



Refractory epilepsy is associated with high costs that affect individuals and society. Costs differ across centers in relation to the characteristics of patients and the extent of use of more expensive, second-generation AEDs. Epilepsy-specific costs cannot be easily differentiated from costs related to comorbidities.
Inhaled synthetic surfactant abolishes the early allergen-induced response in asthma.

Allergen-induced inhibition of pulmonary surfactant in asthma may promote airway oedema and consequently potentiate the severity of the asthmatic response. A randomised, single-blind, cross-over study of an inhaled synthetic phospholipid dry-powder surfactant (Pumactant) was conducted in atopic, asthmatic subjects with previously documented early and late asthmatic responses (EAR and LAR) to an inhaled allergen. This was conducted to evaluate the role of exogenous surfactant administration on EAR and LAR. A total of seven subjects had complete evaluable data and received the full dose of Pumactant. Asthmatic subjects inhaled two separate doses of 400 mg Pumactant prior to an allergen exposure. The first dose was administered 8 h in advance and the second dose 30 min in advance. The dosage occurred through a purpose-built administration device. This was followed by a standard bronchial-provocation test, and forced expiratory volume in one second (FEV1) was measured at regular intervals over a 10-h period. Pumactant was well tolerated and, surprisingly, abolished the EAR but not the LAR in all seven subjects. The mean area under the curve between 0-2 h (EAR) following bronchial provocation test was 0.08 for the Pumactant treatment group (PT) and 13.29 for the no treatment (NT) group. The maximum drop in FEV1 for EAR was 4.19% and 23.98% in the PT and the NT group, respectively. The demonstration of inhibition of the early asthmatic response by exogenous surfactant, provides the first evidence that pulmonary surfactant dysfunction may also contribute to the very early asthmatic response to allergen. Exogenous surfactant administration could serve as a useful adjunct in controlling the early allergen-induced symptoms in patients with allergic asthma.
Posterior reversible encephalopathy syndrome in a child with post-transplant HHV-6B encephalitis

Allo-SCT with reduced-intensity conditioning (RIC) results in lower non-relapse mortality (NRM), but higher relapse rate than myeloablative conditioning (MAC) in AML/myelodysplastic syndromes (MDS). Novel regimens with intensive anti-leukemic activity, but with limited toxicity will be of benefit. In all, 85 patients with AML/MDS, not eligible for MAC, were given fludarabine-treosulfan conditioning (FT). Outcomes were compared with those in patients given fludarabine-BU RIC (FB2, n1⁄4 106) or reduced-toxicity (RTC) conditioning (FB4, fludarabine and myeloablative BU dose, n1⁄4 85). The 5-year NRM was 29%, 20% and 18% after FT, FB2 and FB4, respectively (P1⁄4NS). Multivariate analysis (MVA) identified comorbidity score (HCT-CI) 42 and advanced disease as adverse factors with no independent impact of regimen. The 5-year relapse rate was 36%, 47% and 40%, respectively (P1⁄4 0.17). MVA identified advanced disease as the major adverse factor, while FT had significantly lower relapse rate (hazard ratio 0.6, P1⁄4 0.03). The 5-year survival (OS) was 37% with advanced disease. HCT-CI 42 and age X50 were found as adverse factors. The 5-year OS was 46%, 44% and 50% after FT, FB2 and FB4 in early-intermediate-stage disease (P1⁄4NS) and 33%, 9% and 28% in advanced disease, respectively (P1⁄4 0.02). FT is an RTC regimen with intensive anti-leukemia effect in MAC non-eligible patients.
DIVA: A Reliable Substrate for Deep Submicron Microarchitecture Design

Building a high-performance microprocessor presents many reliability challenges. Designers must verify the correctness of large complex systems and construct implementations that work reliably in varied (and occasionally adverse) operating conditions. To further complicate this task, deep submicron fabrication technologies present new reliability challenges in the form of degraded signal quality and logic failures caused by natural radiation interference.
In this paper, we introduce dynamic verification, a novel microarchitectural technique that can significantly reduce the burden of correctness in microprocessor designs. The approach works by augmenting the commit phase of the processor pipeline with a functional checker unit. The functional checker verifies the correctness of the core processor's computation, only permitting correct results to commit. Overall design cost can be dramatically reduced because designers need only verify the correctness of the checker unit.
We detail the DIVA checker architecture, a design optimized for simplicity and low cost. Using detailed timing simulation, we show that even resource-frugal DIVA checkers have little impact on core processor performance. To make the case for reduced verification costs, we argue that the DIVA checker should lend itself to functional and electrical verification better than a complex core processor. Finally, future applications that leverage dynamic verification to increase processor performance and availability are suggested.
Psychometric properties of the WeeFIM in children with cerebral palsy in Turkey.

The Functional Independence Measure for Children (WeeFIM) instrument has recently been adapted and validated for non-disabled children in Turkey. The aim of this study was to validate the instrument in children with cerebral palsy (CP). One hundred and thirty-four children with CP were assessed using the WeeFIM. Reliability was tested by internal consistency, intraclass and interrater correlation coefficients (ICCs), internal construct validity by Rasch analysis, and external construct validity by correlation with the Denver II Development Test (Denver II). Mean age of the participants (70 females, 64 males) was 4y 6mo (SD 3y 8mo, range 6mo-16y). CP type was: diplegia in 37.3%, hemiplegia in 20.2%, quadriplegia in 8.2%, 'baby at risk' (i.e. infants who show neuromotor delay but cannot be classified in a CP type) in 29.9%, and other in 4.5%. Reliability of the WeeFIM was excellent with high Cronbach's alpha and ICC values ranging between 0.91 and 0.98 for the motor and cognitive scales. After collapsing response categories, both motor and cognitive scales met Rasch model expectations. Unidimensionality of the motor scale was confirmed after adjustment for local dependency of items. There was no substantive differential item functioning and strict unidimensionality for both scales was shown by analysis of the residuals. External construct validity was supported by expected high correlations with developmental ages determined by the social, fine motor function, language, and gross motor function domains of the Denver II. We conclude that the WeeFIM is a reliable and valid instrument for evaluating the functional status of Turkish children with CP.