nils-herrmann/clean_scirepeval huggingface dataset:
Multicenter phase 1 trial of intraventricular immunochemotherapy in recurrent CNS lymphoma.

Recurrent CNS lymphoma continues to be associated with poor outcomes in the rituximab era. Although IV rituximab mediates superior disease control of systemic non-Hodgkin lymphoma (NHL), it fails to completely eliminate the risk of meningeal recurrence, likely due to minimal CNS penetration. Given that rituximab acts synergistically with chemotherapy, we conducted the first phase 1 study of intraventricular immunochemotherapy in patients with recurrent CNS NHL. Fourteen patients received 10 mg or 25 mg intraventricular rituximab twice weekly for 4 weeks, with rituximab administered as monotherapy during the first treatment each week and rituximab administered in combination with methotrexate (MTX) during the second treatment each week. More than 150 doses were administered without serious toxicity. In a population with high-refractory CNS NHL, 75% of patients achieved complete cytologic responses and 43% achieved an overall complete response in CSF and/or brain parenchyma. Two patients achieved a first complete response of CNS NHL with intraventricular rituximab/MTX, including 1 with CNS lymphoma refractory to high-dose systemic and intrathecal MTX plus IV rituximab. We conclude that intraventricular rituximab in combination with MTX is feasible and highly active in the treatment of drug-resistant CNS NHL that is refractory or unresponsive to IV rituximab.



Phase I study showed that intraventricular rituximab plus methotrexate is feasible and active in the treatment of refractory CNS lymphoma.
HMM-based methods for channel error mitigation in distributed speech recognition

Distributed Speech Recognition involves the development of techniques to mitigate the degradations that the transmission channel introduces in the speech features. This work proposes an HMM framework from which different mitigation techniques oriented to bursty channels can be derived. In particular, two MMSE-based and a new Viterbi-based mitigation procedures are derived under this framework. Several implementation issues such as the channel SNR estimation or the application of hard decision on the received signal vectors are dealt with. Also, different boundary conditions suitable for the speech recognition application are studied for the different mitigation procedures. The experimental results show that the HMM-based techniques can effectively mitigate channel errors, even in very poor channel conditions.
Effect of low-level HCV viraemia at week 24 on HCV treatment response in genotype 1 patients.

We examined the detection of low-level viraemia at week 24 as a predictor of sustained virological response (SVR) and viral relapse/breakthrough, and the agreement between the Roche Cobas TaqMan™ HCV RNA assay (TaqMan) and Roche Cobas(®) Amplicor HCV qualitative assay (Amplicor; both Roche Molecular Diagnostics, Pleasanton, CA, USA) for detection of low-level viraemia.



A total of 871 treatment-naive HCV genotype 1 patients participating in an induction-dose pegylated interferon therapy study had virological responses assessed using TaqMan. A total of 151 patients with HCV RNA levels ≤500 IU/ml had samples tested in parallel using the Amplicor and TaqMan assays.



SVR was significantly lower and relapse/breakthrough significantly higher in patients with low-level residual viraemia at week 24 compared with those who had undetectable viraemia: SVR was 72%, 29% and 14% (P<0.0001) and relapse/breakthrough 28%, 71% and 86% (P<0.0001) in patients with viraemia that was undetectable, detectable <15 IU/ml and detectable 15-<50 IU/ml, respectively, at week 24. The negative predictive value (NPV) for a week-24 virological response for SVR was 86%, 90% and 90% using TaqMan cutoffs of undetectable, <15 IU/ml and <50 IU/ml, respectively. The percentage agreement between Amplicor and TaqMan was similarly high for TaqMan cutoffs of 50 IU/ml and 15 IU/ml, but lower for undetectable viraemia (83%, 83% and 70%, respectively).



These data emphasize the importance of achieving undetectable HCV RNA during pegylated interferon therapy to maximize SVR; however, the current 24-week stopping rule of undetectable HCV RNA appears too stringent when using sensitive PCR assays given the observed lower NPV for SVR using the TaqMan undetectable cutoff. Our data also suggest that a TaqMan <15 IU/ml result is comparable to an Amplicor-negative result (that is, below the assay cutoff value) when monitoring viral response.
LV dyssynchrony as assessed by phase analysis of gated SPECT myocardial perfusion imaging in patients with Wolff-Parkinson-White syndrome

The purpose of this study was to evaluate left ventricular (LV) mechanical dyssynchrony in patients with Wolff-Parkinson-White (WPW) syndrome pre- and post-radiofrequency catheter ablation (RFA) using phase analysis of gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). Forty-five WPW patients were enrolled and had gated SPECT MPI pre- and 2–3 days post-RFA. Electrophysiological study (EPS) was used to locate accessory pathways (APs) and categorize the patients according to the AP locations (septal, left and right free wall). Electrocardiography (ECG) was performed pre- and post-RFA to confirm successful elimination of the APs. Phase analysis of gated SPECT MPI was used to assess LV dyssynchrony pre- and post-RFA. Among the 45 patients, 3 had gating errors, and thus 42 had SPECT phase analysis. Twenty-two patients (52.4 %) had baseline LV dyssynchrony. Baseline LV dyssynchrony was more prominent in the patients with septal APs than in the patients with left or right APs (p < 0.05). RFA improved LV synchrony in the entire cohort and in the patients with septal APs (p < 0.01). Phase analysis of gated SPECT MPI demonstrated that LV mechanical dyssynchrony can be present in patients with WPW syndrome. Septal APs result in the greatest degree of LV mechanical dyssynchrony and afford the most benefit after RFA. This study supports further investigation in the relationship between electrical and mechanical activation using EPS and phase analysis of gated SPECT MPI.
Optimization and validation of a SPE-HPLC-PDA-fluorescence method for the simultaneous determination of drugs used in combined cardiovascular therapy in human plasma.

This paper reports the chemometrical optimization and the validation of a quantitative high performance liquid chromatography-photodiode array-fluorescence (HPLC-PDA-Fluo) method for the simultaneous analysis, in human plasma, of drugs usually combined in cardiovascular therapy. Separation of chlorthalidone (CLTD), valsartan (VAL), valsartan-M1 (VAL-M1), fluvastatin (FLUV) and the internal standard (IS) candesartan cilexetil was performed on a dC18 Atlantis column (100 mm x 3.9 mm, 3 microm) using a gradient with a run time of 15 min. The mobile phase consisted of a mixture of acetonitrile and water containing 0.01% of formic acid and 10 mM of ammonium formate at pH 4.1. UV and fluorimetric (valsartan, its metabolite and fluvastatin) detectors were used. The sample preparation consisted of protein precipitation using acetonitrile suited to a solid-phase extraction (SPE) on a Strata-X cartridge for sample clean-up. Method validation was developed following the recommendations for bioanalytical method validation of International Conference on Harmonisation (ICH) and Food and Drug Administration (FDA) organizations. The method showed good linearity (31-3000 microg/l for chlorthalidone, 20-1000 microg/l for valsartan-M1, 10-5000 microg/l for valsartan and 14-1000 microg/l for fluvastatin), precision and accuracy. Recoveries were in the range of 78-91%. This method allowed the determination of these drugs in human plasma samples obtained from patients under cardiovascular treatment.
The combination of bendamustine, bortezomib, and rituximab for patients with relapsed/refractory indolent and mantle cell non-Hodgkin lymphoma.

Given the significant activity and tolerability of bendamustine, rituximab, and bortezomib in patients with relapsed indolent and mantle cell non-Hodgkin lymphoma, and laboratory studies suggesting synergistic activity, we conducted a multicenter phase 2 study of the bendamustine/bortezomib/rituximab combination. Patients with relapsed or refractory indolent and mantle cell lymphoma with adequate organ function were treated with bendamustine 90 mg/m² days 1 and 4; rituximab 375 mg/m² day 1, and bortezomib 1.3 mg/m² days 1, 4, 8, 11. Six 28-day cycles were planned. Thirty patients (7 with mantle cell lymphoma) were enrolled and treated. Eight patients experienced serious adverse events, including one event of grade 5 sepsis. Common nonhematologic adverse events were generally grade 1 or grade 2 and included nausea (50%), neuropathy (47%), fatigue (47%), constipation (40%), and fever (40%). Of 29 patients evaluable for efficacy, 24 (83%) achieved an objective response (including 15 with complete response). With median follow-up of 24 months, 2-year progression-free survival is 47% (95% confidence interval, 25%-69%). On the basis of these promising results, the US cooperative groups have initiated randomized trials to evaluate this regimen in follicular and mantle cell lymphoma.
Gene Variant of the Bradykinin B2 Receptor Influences Pulmonary Arterial Pressures in Heart Failure Patients

Pulmonary arterial pressure (PAP) varies considerably in heart failure (HF) despite similar degrees of left ventricular (LV) dysfunction. Bradykinin alters vascular tone and common variations in the kinin B2 receptor (BDKRB2) gene exists. We hypothesized that genetic variation in this receptor would influence PAP in HF.  131 HF patients (>1yr history systolic HF), without COPD, not currently smoking, BMI < 40, without atrial fibrillation completed the study which included a blood draw for genotyping and neurohormones (ACE, A-II, Bradykinin, ANP, BNP, and catecholamines), an echocardiogram for cardiac function and systolic PAP (PAPsys).  Mean LVEF was 29% ± 12%, NYHA class 2 ± 1, age 56 ± 12 yr, BMI 28 ± 5 kg/m(2). Forty-six patients (35%) were homozygous for the +9 allele, 58 (44%) were heterozygous (+9/-9) and 27 (21%) were homozygous for the -9 allele of the BDKRB2. PAPsys averaged 42 ± 13, 38 ± 12, and 35 ± 11 mmHg for +9/+9, +9/-9 and -9/-9, respectively (p = 0.03). There was a trend towards gene effect for plasma ACE with the highest values in +9/+9 and lowest in -9/-9 patients (9.5 ± 10.7, 7.1 ± 8.7, and 5.4 ± 6.4 U/L, respectively, p = 0.06). There were no differences in plasma bradykinin or A-II, LVEF, or NYHA across genotypes.  These data suggest the +9/+9 polymorphism of the BDKRB2 receptor influences pulmonary vascular tone in stable HF.
Morphological Abnormalities of Thalamic Subnuclei in Migraine: A Multicenter MRI Study at 3 Tesla.

The thalamus contains third-order relay neurons of the trigeminal system, and animal models as well as preliminary imaging studies in small cohorts of migraine patients have suggested a role of the thalamus in headache pathophysiology. However, larger studies using advanced imaging techniques in substantial patient populations are lacking. In the present study, we investigated changes of thalamic volume and shape in a large multicenter cohort of patients with migraine. High-resolution T1-weighted MRI data acquired at 3 tesla in 131 patients with migraine (38 with aura; 30.8 ± 9 years old; 109 women; monthly attack frequency: 3.2 ± 2.5; disease duration: 14 ± 8.4 years) and 115 matched healthy subjects (29 ± 7 years old; 81 women) from four international tertiary headache centers were analyzed. The thalamus and thalamic subnuclei, striatum, and globus pallidus were segmented using a fully automated multiatlas approach. Deformation-based shape analysis was performed to localize surface abnormalities. Differences between patients with migraine and healthy subjects were assessed using an ANCOVA model. After correction for multiple comparisons, performed using the false discovery rate approach (p < 0.05 corrected), significant volume reductions of the following thalamic nuclei were observed in migraineurs: central nuclear complex (F(1,233) = 6.79), anterior nucleus (F(1,237) = 7.38), and lateral dorsal nucleus (F(1,238) = 6.79). Moreover, reduced striatal volume (F(1,238) = 6.9) was observed in patients. This large-scale study indicates structural thalamic abnormalities in patients with migraine. The thalamic nuclei with abnormal volumes are densely connected to the limbic system. The data hence lend support to the view that higher-order integration systems are altered in migraine.



This multicenter imaging study shows morphological thalamic abnormalities in a large cohort of patients with episodic migraine compared with healthy subjects using state-of-the-art MRI and advanced, fully automated multiatlas segmentation techniques. The results stress that migraine is a disorder of the CNS in which not only is brain function abnormal, but also brain structure is undergoing significant remodeling.
Decreasing cardiovascular risk factors in obese individuals using a combination of PGX® meal replacements and PGX® granules in a 12-week clinical weight modification program.

In this open, clinically based, weight modification program, we determined in six sedentary obese adults (five women; one male; age range 30-62 years) that the combination of a modified calorie diet plus PGX® meal replacement and PGX® supplementation resulted in a significant reduction in several cardiovascular risk factors over a 12-week time period. This included a significant improvement in lipids (-0.98 mmol/l LDL-C), reduction in average weight (-9.2 kg), mean reduction in fat (-4.1%) and an increase in fat-free mass (2.8%).
A new self-completion outcome measure for diabetes: is it responsive to change?

Self-completion instruments assessing subjective health are increasingly being used to measure patient outcome. However, there is very little evidence as yet of existing instruments' responsiveness to change. This paper describes a study to evaluate the responsiveness to change of a self-completion instrument for the measurement of clinical outcome in patients with diabetes. A prospective follow-up study of 48 patients with non-insulin-dependent diabetes commencing insulin therapy was carried out, with assessments at baseline (i.e. pre-intervention), 6 weeks and 3 months post-intervention. The outcome measures used were the changes in scores on the self-completion instrument for symptom level, physical function, energy, depression, psychological distress and barriers to activity, HbA1c, non-fasting serum cholesterol and the body mass index (BMI). There were significant improvements in HbA1c and non-fasting serum cholesterol and worsening of the BMI, as expected. The self-completion instrument detected significant improvements in patient-reported symptoms within 6 weeks of the intervention (p<0.01) and in energy levels (p<0.05). There is evidence from this study of the self-completion instrument's ability to respond to change and it has potential for use in evaluative studies.
Exploring ART Intake Scenes in a Human Rights-Based Intervention to Improve Adherence: A Randomized Controlled Trial

To assess the effectiveness of a psychosocial individual intervention to improve adherence to ART in a Brazilian reference-center, consenting PLHIV with viral load >50 copies/ml were selected. After 4 weeks of MEMS cap use, participants were randomized into an intervention group (IG) (n = 64) or control group (CG) (n = 57). CG received usual care only. The IG participated in a human rights-based intervention approach entailing four dialogical meetings focused on medication intake scenes. Comparison between IG and CG revealed no statistically significant difference in adherence measured at weeks 8, 12, 16, 20 and 24. Viral load (VL) decreased in both groups (p < 0.0001) with no significant difference between study groups. The lower number of eligible patients than expected underpowered the study. Ongoing qualitative analysis should provide deeper understanding of the trial results.  Tras 4 semanas de uso de MEMS caps, los participantes fueron aleatorizados en el grupo de intervención (GI) (n = 64) o el grupo control (GC) (n = 57). El CG recibió solamente los cuidados habituales. El GI participó de una intervención basada en los derechos humanos, con cuatro reuniones dialógicas centradas en escenas de toma de medicamentos. La comparación entre GI y CG no reveló ninguna diferencia estadísticamente significativa en la adhesión medida en las semanas 8, 12, 16, 20 y 24. La carga viral (CV) disminuyó en ambos grupos del estudio (p < 0.0001), aunque sin significado estadístico. El número de pacientes elegibles, más pequeño del que el esperado, disminuyó el poder del estudio. El análisis cualitativo actual debe proporcionar una comprensión más profunda de los resultados del estudio. Registro del Ensayo Clínico: NCT00716040.
Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of paroxysmal atrial fibrillation (RAAFT-2): a randomized trial.

Atrial fibrillation (AF) is the most common rhythm disorder seen in clinical practice. Antiarrhythmic drugs are effective for reduction of recurrence in patients with symptomatic paroxysmal AF. Radiofrequency ablation is an accepted therapy in patients for whom antiarrhythmic drugs have failed; however, its role as a first-line therapy needs further investigation.



To compare radiofrequency ablation with antiarrhythmic drugs (standard therapy) in treating patients with paroxysmal AF as a first-line therapy.



A randomized clinical trial involving 127 treatment-naive patients with paroxysmal AF were randomized at 16 centers in Europe and North America to received either antiarrhythmic therapy or ablation. The first patient was enrolled July 27, 2006; the last patient, January 29, 2010. The last follow-up was February 16, 2012.



Sixty-one patients in the antiarrhythmic drug group and 66 in the radiofrequency ablation group were followed up for 24 months.



The time to the first documented atrial tachyarrhythmia of more than 30 seconds (symptomatic or asymptomatic AF, atrial flutter, or atrial tachycardia), detected by either scheduled or unscheduled electrocardiogram, Holter, transtelephonic monitor, or rhythm strip, was the primary outcome. Secondary outcomes included symptomatic recurrences of atrial tachyarrhythmias and quality of life measures assessed by the EQ-5D tool.



Forty-four patients (72.1%) in the antiarrhythmic group and in 36 patients (54.5%) in the ablation group experienced the primary efficacy outcome (hazard ratio [HR], 0.56 [95% CI, 0.35-0.90]; P = .02). For the secondary outcomes, 59% in the drug group and 47% in the ablation group experienced the first recurrence of symptomatic AF, atrial flutter, atrial tachycardia (HR, 0.56 [95% CI, 0.33-0.95]; P = .03). No deaths or strokes were reported in either group; 4 cases of cardiac tamponade were reported in the ablation group. In the standard treatment group, 26 patients (43%) underwent ablation after 1-year. Quality of life was moderately impaired at baseline in both groups and improved at the 1 year follow-up. However, improvement was not significantly different among groups.



Among patients with paroxysmal AF without previous antiarrhythmic drug treatment, radiofrequency ablation compared with antiarrhythmic drugs resulted in a lower rate of recurrent atrial tachyarrhythmias at 2 years. However, recurrence was frequent in both groups.
Phase I study of intermittent oral dosing of the insulin-like growth factor-1 and insulin receptors inhibitor OSI-906 in patients with advanced solid tumors.

We determined the maximum tolerated dose (MTD), safety, pharmacokinetics, pharmacodynamics, and preliminary activity of OSI-906, a potent, oral, dual inhibitor of insulin-like growth factor-1 receptor (IGF1R) and insulin receptor (IR), in patients with advanced solid tumors.



This was a multicenter, open-label, dose escalation phase I study evaluating three intermittent dosing schedules of once-daily OSI-906 [schedule (S) 1, days 1-3 every 14 days; S2, days 1-5 every 14 days; S3, days 1-7 every 14 days]. A fed-fasting expansion cohort was included in the study.



Seventy-nine patients were enrolled: 62 in S1, 4 in S2, and 13 in S3. S2 was discontinued. Dose-limiting toxicity comprised grade 3-4 hyperglycemia, vomiting, fatigue, and prolonged QTc interval. The MTD and recommended phase II dose of OSI-906 was 600 mg for both S1 and S3 schedules. Other common adverse events were grade 1-2 nausea, vomiting, fatigue, and diarrhea. The pharmacokinetics of OSI-906 was dose linear, and the terminal half-life ranged between 2 and 6 hours. High-fat meals had a moderate effect on the pharmacokinetics of OSI-906. At the MTD, inhibition of IGF1R and IR was observed in peripheral blood mononuclear cells. An increase in plasma IGF1 concentrations, an indirect measure of IGF1R signaling inhibition, was seen at doses ≥ 450 mg. Two patients with adrenocortical carcinoma achieved partial responses.



The MTD of 600 mg was well tolerated and associated with preliminary antitumor activity. These data support further evaluation of OSI-906 in solid tumors.
Dry Eye Syndrome Risks in Patients With Fibromyalgia

The coexistence of fibromyalgia (FM) and dry eye syndrome (DES) has been previously reported. However, there are few studies on how patients with FM may develop concomitant DES. Patients with chronic widespread pain, like FM, chronic fatigue syndrome, and irritable bowel syndrome (IBS), was concerned for the rheumatic or psychosomatic disorders which might adequately reflect the long-term risk of DES. We retrieved data on FM patients from the National Health Insurance Research Database of Taiwan covering the years 2000 to 2011. Our FM population consisted of 25,777 patients versus 103,108 patients in the non-FM group: the overall incidence of DES in these populations was 7.37/10,000 and 4.81/10,000, respectively. Male FM patients had a higher incidence of DES, with a 1.39-fold DES risk for males and a 1.45-fold for females after adjustment for confounding factor. Notably, FM patients aged ≤49 years had an elevated 80% risk of DES compared with the non-FM group. Without comorbidities, FM patients had an approximately 1.40-fold risk of DES than those without FM. The additive effects of FM and IBS or FM and sleep disturbance were pointed out that the risk for DES would be elevated when the FM patients with IBS or sleep disturbance. FM patients have a higher incidence of DES than that of non-FM patients. They carry long-term DES risks from a relatively young age, particularly those with psychiatric problems. Risk stratification for a timely psychiatric medication intervention and risk modifications are not intended.