nils-herrmann/clean_scirepeval huggingface dataset:
Enlarged Memory T-Cell Pool and Enhanced Th1-Type Responses in Chronic Myeloid Leukemia Patients Who Have Successfully Discontinued IFN-α Monotherapy

A small proportion of chronic myeloid leukemia patients treated with interferon-α (IFN-α) monotherapy are able to discontinue the treatment without disease relapse although residual leukemia cells are present. Recently, we showed that these patients have increased amount of NK-cells and a distinct blood cytokine profile. We now aimed to study the function of NK- and T-cells in order to understand the role of the immune system in maintaining the treatment response after IFN-α discontinuation. The study included 13 patients: 5 patients were still treated with IFN-α monotherapy (IFN-ON, median treatment time 163 months) and 8 had stopped the treatment successfully (IFN-OFF, median time without therapy 42 months). Detailed immunophenotype and cytokine production of NK- and T-cells was analyzed with flow cytometry. In addition, the cytotoxicity of NK-cells was studied using K562 as target cells and both the degranulation and direct killing was measured. Compared to healthy controls, IFN-OFF patients had increased proportion of CD4(+) effector memory (CCR7(-)CD45RA(-); median 23% vs. healthy 16%, p = 0.009) and CD8(+) central memory T-cells (CCR7(+)CD45RA(-); median 26% vs. healthy 14%, p = 0.004). Further, upon stimulation the IFN-γ/TNF-α cytokine secretion by CD4(+) T-cells was significantly enhanced in IFN-OFF patients (median 13.7% vs. healthy 7.8%, p = 0.01), and CD4+ effector and central memory cells were the main cytokine producers. No similar increase was observed in IFN-ON group (6.5%). In addition, the proportion of NK-cells was significantly increased in IFN-OFF patients (median IFN-OFF 24%, healthy 13%, p = 0.04), but their direct killing of K562 cells was impaired. The cytotoxicity of NK-cells was also diminished in IFN-ON patients. To conclude, in addition to elevated NK-cell count, IFN-OFF patients have increased amount of memory T-cells, which are able to induce strong cytokine response upon stimulation. This activity may contribute to the maintenance of prolonged remission after successful IFN-α discontinuation.
Does Erythropoietin Cause Hemoglobin Variability- Is It ‘Normal’?

Hemoglobin variability (Hb-var) in patients with chronic kidney disease has been stipulated to be a result of exogenous treatment with erythropoiesis stimulating agents (ESA) and has been related to mortality in dialysis patients. We hypothesized the existence of Hb-var independent of ESA administration and compared it to that in healthy adults using data from the Scripps-Kaiser and NHANES III databases. We studied the Hb-var in 1571 peritoneal dialysis patients which included 116 patients not requiring treatment with erythropoietin. We systematically studied the differences between the groups that needed ESA therapy and those who did not. White race and male sex were significant predictors of need for erythropoietin therapy. We found peritoneal dialysis patients to exhibit significantly increased Hb-var independent of treatment with exogenous erythropoietin (0.99 gm/dL vs. 1.17 gm/dL, p-value<0.001). We found age to be a significant determinant of Hb-var in the ESA treated group. Hb-var in younger patients (<30 years) was increased by 50% compared to young healthy adults. The Hb-var in elderly (>60 years) peritoneal dialysis patients was similar to that seen in healthy elders, suggesting similarity with anemia of aging. We conclude that exogenous ESA administration does not explain Hb-var entirely but may enhance it. Intrinsic factors affecting erythropoiesis including age may be the major determinants of Hb-var.
Family-Responsive Psychoeducation Groups for Families with an Adult Member with Mental Illness: Pilot Results

This paper documents recent pilot efforts of the Psychoeducation Responsive to Family (PERF) model, a yearlong group for families with an adult member coping with mental illness. PERF advances state-of-the-art in its: (a) application in community settings; (b) utility for families coping with all types of mental illness; (c) use of a standardized model, yet retaining a flexible curriculum responsive to family group membership concerns; and (d) recruitment from one-day family workshops of participants eager to further explore their issues. This report examines changes in these families' knowledge and mastery in a small random assignment study comparing the PERF model (n = 9) with a “usual services” (n = 10) condition. Study participants completed surveys measuring perceived mastery and knowledge at baseline and at 3, 6, and 12 months for both conditions. Families in the active PERF intervention demonstrated significant post-intervention improvements in four of five variables analyzed. For one of these items, PERF demonstrated significantly greater improvement than the usual care condition. Achievement of significant changes in these measures was examined in relation to timing of presentation of curriculum topics in the groups. Gains in perceived crisis effectiveness temporally correlated with coverage of that topic in the PERF groups, while gains in other items were instead steadily cumulative across the entire year. The encouraging results of this second pilot effort serve to substantiate the initial efforts in developing the PERF group model.
Patients With Combined Membranous Nephropathy and Focal Segmental Glomerulosclerosis Have Comparable Clinical and Autoantibody Profiles With Primary Membranous Nephropathy

Patients with combined membranous nephropathy (MN) and focal segmental glomerulosclerosis (FSGS) have been reported with different clinical significance. Investigations on the possible mechanisms of the combined glomerular lesions are necessary but scarce. Twenty patients with both MN and FSGS lesions were enrolled in the study. Sixty-five patients with primary MN and 56 patients with primary FSGS were used as disease controls. Clinical data on renal biopsy and during follow-up were collected. Circulating anti-phospholipase A2 receptor (PLA2R) antibody, glomerular PLA2R expression, IgG4 deposition, and soluble urokinase receptor (suPAR) levels were detected. We found that patients with combined lesions presented with older age, less proteinuria, higher albumin, and better renal function on biopsy. These were comparable to the patients with primary MN, but differed from the patients with primary FSGS. Patients with combined lesions showed higher stages of MN, no cellular variant on FSGS classification, and more common (100.0%) tubulointerstitial injury than both primary MN and primary FSGS patients. In the patients with combined lesions, 80.0% had circulating anti-PLA2R antibody and 68.4% had IgG4 predominant deposition in glomeruli, which were comparable to primary MN. The patients with combined lesions had significantly lower urinary suPAR concentrations, than the primary FSGS patients (315.6 ± 151.0 vs 752.1 ± 633.9 pg/μmol; P = 0.002), but similar to the primary MN patients (267.9 ± 147.5 pg/μmol). We conclude that patients with combined MN and FSGS may share the same underlying pathogenesis with primary MN. The FSGS lesion might be secondary to primary MN.
Decreased heart rate variability may predict the progression of carotid atherosclerosis in type 2 diabetes

Heart rate variability (HRV), a measure of autonomic function, can predict survival outcomes. Cardiovascular disease is a known complication of diabetes, and we aimed to determine if autonomic dysfunction was associated with carotid artery atherosclerotic plaques in type 2 diabetic patients. We assessed frequency domain HRV from power spectral analysis of 24 h Holter ECG recordings, expiration/inspiration (E/I) ratio during deep breathing, acceleration index (AI) of R–R interval in response to head-up tilt, and the degree of carotid artery atherosclerosis in 61 type-2 diabetic patients (39 males, 45–69 years). Studies were carried out 5–6 years after diagnosis (baseline) and repeated 8 years after diagnosis (follow-up). At baseline, patients diagnosed with autonomic neuropathy, with abnormal E/I ratio and abnormal AI measurements, had decreased low frequency (LF) HRV. Baseline E/I ratio correlated with day (r = 0.34; P < 0.001) and night-time (r = 0.44; P < 0.001) LF power. Night-time HRV did not differ in patient with and without autonomic neuropathy. Reduced common carotid artery diameter and atherosclerotic intima-media thickness (IMT) both correlated with HRV at baseline. At follow-up, all HRV variables decreased significantly. Furthermore, patients with lower LF power at baseline, had a larger increase in the thickness of the carotid bulb intima-media at follow-up. Our results show that LF HRV power is associated with the extent and progression of carotid atherosclerosis in type 2 diabetes. A low LF HRV may predict the progression of atherosclerosis in these patients.
Comparison of myocardial contrast echocardiography with NC100100 and (99m)Tc sestamibi SPECT for detection of resting myocardial perfusion abnormalities in patients with previous myocardial infarction.

To determine whether myocardial contrast echocardiography (MCE) following intravenous injection of perfluorocarbon microbubbles permits identification of resting myocardial perfusion abnormalities in patients who have had a previous myocardial infarction.



22 patients (mean (SD) age 66 (11) years) underwent MCE after intravenous injection of NC100100, a novel perfluorocarbon containing contrast agent, and resting (99m)Tc sestamibi single photon emission computed tomography (SPECT). With both methods, myocardial perfusion was graded semiquantitatively as 1 = normal, 0.5 = mild defect, and 0 = severe defect.



Among the 203 normally contracting segments, 151 (74%) were normally perfused by SPECT and 145 (71%) by MCE. With SPECT, abnormal tracer uptake was mainly found among normally contracting segments from the inferior wall. By contrast, with MCE poor myocardial opacification was noted essentially among the normally contracting segments from the anterior and lateral walls. Of the 142 dysfunctional segments, 87 (61%) showed perfusion defects by SPECT, and 94 (66%) by MCE. With both methods, perfusion abnormalities were seen more frequently among akinetic than hypokinetic segments. MCE correctly identified 81/139 segments that exhibited a perfusion defect by SPECT (58%), and 135/206 segments that were normally perfused by SPECT (66%). Exclusion of segments with attenuation artefacts (defined as abnormal myocardial opacification or sestamibi uptake but normal contraction) by either MCE or SPECT improved both the sensitivity (76%) and the specificity (83%) of the detection of SPECT perfusion defects by MCE.



The data suggest that MCE allows identification of myocardial perfusion abnormalities in patients who have had a previous myocardial infarction, provided that regional wall motion is simultaneously taken into account.
Fully automatic diagnostic system for early- and late-onset mild Alzheimer’s disease using FDG PET and 3D-SSP

The purpose of this study was to design a fully automatic computer-assisted diagnostic system for early- and late-onset mild Alzheimer’s disease (AD). Glucose metabolic images were obtained from mild AD patients and normal controls using positron emission tomography (PET) and 18F-fluorodeoxyglucose (FDG). Two groups of 20 mild AD patients with different ages of onset were examined. A fully automatic diagnostic system using the statistical brain mapping method was established from the early-onset (EO) and late-onset (LO) groups, with mean ages of 59.1 and 70.9 years and mean MMSE scores of 23.3 and 22.8, respectively. Aged-matched normal subjects were used as controls. We compared the diagnostic performance of visual inspection of conventional axial FDG PET images by experts and beginners with that of our fully automatic diagnostic system in another 15 EO and 15 LO AD patients (mean age 58.4 and 71.7, mean MMSE 23.6 and 23.1, respectively) and 30 age-matched normal controls. A receiver operating characteristic (ROC) analysis was performed to compare data. The diagnostic performance of the automatic diagnostic system was comparable with that of visual inspection by experts. The area under the ROC curve for the automatic diagnostic system was 0.967 for EO AD patients and 0.878 for LO AD patients. The mean area under the ROC curve for visual inspection by experts was 0.863 and 0.881 for the EO and LO AD patients, respectively. The mean area under the ROC curve for visual inspection by beginners was 0.828 and 0.717, respectively. The fully automatic diagnostic system for EO and LO AD was able to perform at a similar diagnostic level to visual inspection of conventional axial images by experts.
Pharmacokinetics of bendroflumethiazide in hypertensive patients

After four weeks on placebo treatment, 8 hypertensive patients (WHO stage I) were treated for 2 weeks with bendroflumethiazide (bft) 2.5 mg and KCl 1.5 g daily. Subsequently they received bft 5 mg and KCl 1.5 g daily for a further fortnight. At the end of each period of treatment blood pressure was recorded and blood samples and urine were collected for analysis of bft by GLC. Before taking the daily dose of bft, no trace of the drug was found in plasma. Peak levels of bft were seen after 2.3 h and averaged 23 and 50 ng · ml−1 after 2.5 and 5 mg, respectively. After bft 2.5 mg the plasma level was too low for kinetic analysis. The plasma half-life after 5 mg averaged 4.1 h. The mean apparent volume of distribution was 1.18 l · kg−1. Non-renal clearance averaged 200 ml · min−1. The renal clearance of bft was significantly lower (p<0.05) after 5 mg (48 ml · min−1) than after 2.5 mg bft (93 ml · min−1), although the creatinine clearance remained unchanged. No correlation was found between the plasma level of bft and its effect on blood pressure.
Safety and tolerability of NXY-059 for acute intracerebral hemorrhage: the CHANT Trial.

NXY-059 is a free radical-trapping neuroprotectant developed for use in acute ischemic stroke. To facilitate prompt administration of treatment, potentially before neuroimaging, we investigated the safety of NXY-059 in patients with intracerebral hemorrhage (ICH).



We randomized 607 patients within 6 hours of acute ICH to receive 2270 mg intravenous NXY-059 over 1 hour and then up to 960 mg/h over 71 hours, or matching placebo, in addition to standard care. The primary outcome was safety: the mortality and the frequency of adverse events, and the change from baseline for a variety of serum, imaging, and electrophysiological measurements. We also studied the overall distribution of disability scores on the modified Rankin Scale (mRS) and the Barthel index.



We treated 300 patients with NXY-059 and 303 with placebo. Treatment groups were well matched for prognostic variables including Glasgow Coma Scale, risk factors, and age. The mean National Institute of Health Stroke Scale score on admission was 14 in both groups. The baseline hemorrhage volume was 22.4+/-20.1 mL in the NXY-059 group and 23.3+/-22.8 mL in the placebo group (mean+/-SD). Most hemorrhages were related to hypertension or anticoagulant use. Mortality was similar in both groups: 20.3% for NXY-059 and 19.8% for placebo-treated patients. The proportion of patients who experienced an adverse event was the same for both groups, whereas for serious adverse events the proportion was slightly higher in the NXY-059 group. However, no pattern emerged to indicate a safety concern. Serum potassium fell transiently in both groups, lower in the NXY-059 group. There were no differences in 3-month function, disability, or neurological deficit scores. The odds ratio for an improved outcome in 3-month mRS scores in the NXY-059 group was 1.01 (95% CI 0.75, 1.35).



NXY-059 given within 6 hours of acute ICH has a good safety and tolerability profile, with no adverse effect on important clinical outcomes.
2-Deoxy-2[F-18]FDG-PET for Detection of Recurrent Laryngeal Carcinoma after Radiotherapy: Interobserver Variability in Reporting

To evaluate accuracy and interobserver variability in the assessment of 2-deoxy-2[F-18]fluoro-d-glucose-positron emission tomography (FDG-PET) for detection of recurrent laryngeal carcinoma after radiotherapy. Eleven experienced nuclear physicians from eight centres assessed 30 FDG-PET scans on the appearance of local recurrence (negative/equivocal/positive). Conservative (equivocal analysed as negative) and sensitive (equivocal analysed as positive) assessment strategies were compared to the reference standard (recurrence within 6months after PET). Seven patients had proven recurrences. For the conservative and sensitive strategy, the mean sensitivity was 87% and 97%, specificity 81% and 63%, positive predictive values 61% and 46% and negative predictive values 96% and 99%, respectively. Interobserver variability showed a reasonable relation in comparison to the reference standard (kappa = 0.55). FDG-PET has acceptable interobserver agreement and yields good negative predictive value for detection of recurrent laryngeal carcinoma. It could therefore be used as first diagnostic step and may reduce futile invasive diagnostics.
No further gain can be achieved by calculating Disease Activity Score in 28 joints with high-sensitivity assay of C-reactive protein because of high intraindividual variability of C-reactive protein

Disease Activity Score in 28 joints (DAS28) is commonly used to evaluate disease activity of rheumatoid arthritis (RA) and is a guide to treatment decision.The aim of this study was to evaluate the impact of lower reporting limit for C-reactive protein (CRP), with respect to intraindividual biological variability, on the calculation of DAS28 and subsequent patient classification.This study consists of 2 sections: a theoretical consideration discussing the performance of CRP in calculating DAS28 taking intraindividual biological variation and lower reporting limit for CRP into account and a cross-sectional study of RA patients applying our theoretical results. Therefore, we calculated DAS28 twice, with the actual CRP values and CRP = 9 mg/L, the latter to elucidate the positive effects of reducing the lower reporting limit of CRP from <10 to <3 mg/L.Lower-reporting limit of <10 mg/L leads to overestimate DAS28. However, reducing lower reporting limit for CRP to <3 mg/L results in optimizing DAS28 calculation. Further lowering of reporting limit for CRP to <3 mg/L does not increase the precision of DAS28 owing to the relatively large intraindividual biological variation.Five hundred twelve patients were included. There was a significant difference between recalculated and patients DAS28 (P < 0.001). One hundred nine patients had DAS28 deviation (compatible to remission to low: 66, low to moderate: 39. and moderate to high: 4).Owing to significant impact of intraindividual biologic variation on DAS28 and patient classification, special attention should be paid to calculate DAS28 when CRP values are within normal range. Furthermore, we conclude that results of different studies evaluating DAS28 and treatment response are not comparable if the reporting limits of CRP are unknown.
Influence of ionic and non-ionic radiographic contrast media on leukocyte adhesion molecules.

Many papers have focused on the importance of granulocytes in the process of reperfusion and ischemia. Most of the clinical studies measured several parameters of this process during and after coronary angiography, without taking into account the effect of the radiographic contrast media (RCM) used during this procedure.



We performed a randomized patient study (n = 37) to evaluate the effect of ionic and non-ionic RCM on granulocyte adhesion during coronary angiography. We also evaluated the influence of the ionicity and osmolarity of the different substances on granulocyte adhesion molecules in in vitro experiments.



The osmolarity of patient serum samples increased from 302 +/- 1 to 309 +/- 1 mOsm/kg (p < 0.05) after infusion of RCM. The CD11b expression in the samples of the non-ionic RCM treated group increased from 221 +/- 21 MFI to 377 +/- 30 MFI (p < 0.05) measured as the absolute mean fluorescence intensity (MFI), yet did not alter significantly in the ionic RCM group. In contrast, the in vitro experiments showed a reduction of the CD11b expression from 360 +/- 70 MFI to 149 +/- 30 MFI (p < 0.05) in the ionic RCM group.



The upregulation of adhesion molecules was significantly reduced in vivo with ionic RCM, while ionic substances caused opposite effects in vitro. This effect should be taken into account when performing leukocyte functional analysis of samples taken during angiography.
Use of client-specific outcome measures to assess treatment effects in geriatric, arthritic dogs: controlled clinical evaluation of a nutraceutical.

A questionnaire method was designed for dog owners to monitor the orthopedic disabilities of their pets for evaluation of a nutraceutical with joint health claims. Fifty large-breed dogs, 7 to 12 years of age, presenting with signs of osteoarthritis, were randomly allocated to placebo and active treatment groups. Degree of disability was assessed by physical examination, a standard questionnaire on daily activities, and a case-specific questionnaire that monitored specific impairments of each dog. The test product was a special milk protein concentrate (SMPC) from hyperimmunized cows, previously shown to express antiinflammatory and antiarthritic activity in humans. After a 1-week run-in period of dosing with placebo, each dog was randomly assigned to a treatment and given gelatin capsules containing either SMPC or a placebo twice daily for 8 weeks. Overall improvement was noted in 68% and 35% of the SMPC and placebo groups, respectively. Significant (P <.05) improvement in mean standardized and patient- specific questionnaire scores and in owner global assessments was detected in the SMPC group but not in the placebo group. Compared with the placebo group, the treatment response was significantly better in the SMPC group with regard to case-specific scores (P <.001) and owner global assessments (P =.004). The product was well tolerated and serum chemistry findings remained within normal limits.
Internet-based treatment of social phobia: a randomized controlled trial comparing unguided with two types of guided self-help.

Internet-based self-help for social phobia with minimal therapist support via email have shown efficacy in several controlled trials by independent research teams. The role and necessity of therapist guidance is, however, still largely unclear. The present study compared the benefits of a 10-week web-based unguided self-help treatment for social phobia with the same intervention complemented with minimal, although weekly, therapist support via email. Further, a third treatment arm was included, in which the level of support was flexibly stepped up, from no support to email or telephone contact, on demand of the participants. Eighty-one individuals meeting diagnostic criteria for social phobia were randomly assigned to one of the three conditions. Primary outcome measures were self-report measures of symptoms of social phobia. Secondary outcome measures included symptoms of depression, interpersonal problems, and general symptomatology. Measures were taken at baseline, post-treatment, and at 6-month follow-up. Data from a telephone-administered diagnostic interview conducted at post-treatment were also included. Results showed significant symptom reductions in all three treatment groups with large effect sizes for primary social phobia measures (Cohen's d=1.47) and for secondary outcome measures (d=1.16). No substantial and significant between-groups effects were found on any of the measures (Cohen's d=00-.36). Moreover, no difference between the three conditions was found regarding diagnosis-free status, clinically significant change, dropout rates, or adherence measures such as lessons or exercises completed. These findings indicate that Internet-delivered treatment for social phobia is a promising treatment option, whether no support is provided or with two different types of therapist guidance.