nils-herrmann/clean_scirepeval huggingface dataset:
Higher levels of circulating monocyte–platelet aggregates are correlated with viremia and increased sCD163 levels in HIV-1 infection

Increased levels of monocyte–platelet aggregates (MPAs) are reported to be highly correlated with cardiovascular events. In this study, the MPA levels in different monocyte subsets and the associations between MPA levels, HIV-1 viremia and monocyte activation were evaluated during HIV-1 infection. The results showed that the percentages of MPAs in all three monocyte subsets were higher in HIV-1-infected subjects than in healthy controls, and were associated with the plasma viral load in the non-classical and intermediate monocyte subsets. The plasma levels of sCD14 and sCD163 were upregulated in HIV-1 infection and were positively associated with viral loads and negatively associated with CD4 counts. P-selectin glycoprotein ligand-1 (PSGL-1) was shown to be expressed at significantly lower levels on all three monocyte subsets and was negatively correlated with the sCD163 level. The MPA level was correlated with the levels of plasma sCD163 but negatively correlated with CD163 and PSGL-1 on all three monocyte subsets. An elevated immune activation status was correlated with increased MPA formation, underlying the potential interaction between monocyte activation and MPA formation. This interaction may be related to a higher thromboembolic risk in patients infected with HIV-1.Cellular & Molecular Immunology advance online publication, 11 August 2014; doi:10.1038/cmi.2014.66
Variability in the management of nonvariceal upper gastrointestinal bleeding in Europe: an observational study.

Despite recent advances in endoscopic and pharmacological management, nonvariceal upper gastrointestinal bleeding (NVUGIB) is still associated with considerable mortality and morbidity that vary between countries. The European Survey of Nonvariceal Upper Gastrointestinal Bleeding (ENERGiB) reported clinical outcomes across Europe (Belgium, Greece, Italy, Norway, Portugal, Spain, and Turkey) and evaluated management strategies in a "real-world" European setting. This article presents the differences in clinical management strategies among countries participating in ENERGiB.



Adult patients consecutively presenting with overt NVUGIB at 123 participating hospitals over a 2-month period were included. Data relevant to the initial NVUGIB episode and for up to 30 days afterwards were collected retrospectively from patient medical records.



The number of evaluable patients was 2,660; patient demographics and clinical characteristics were similar across countries. There was wide between-country variability in the area and speciality of the NVUGIB management team and unit transfer rates after the initial hospital assessment. The mean time from admission to endoscopy was <1 day only in Italy and Spain. Wide variation in the use of preendoscopy (35.0-88.7%) and relatively consistent (86.5-96.0%) postendoscopic pharmacological therapy rates were observed. There was substantial by-country variability in the rate of therapeutic procedures performed during endoscopy (24.9-47.6%). NVUGIB-related healthcare resource consumption was high and variable (days hospitalized, mean 5.4-8.7 days; number of endoscopies during hospitalization, mean 1.1-1.7).



ENERGiB demonstrates that there are substantial differences in the management of patients with acute NVUGIB episodes across Europe, and that in many cases the guideline recommendations for the management of NVUGIB are not being followed.
Apolipoprotein ε4 modulates phenotype of butyrylcholinesterase in CSF of patients with Alzheimer's disease.

Butyrylcholinesterase K (BCHE-K) is associated with increased risk of developing Alzheimer's disease (AD) in apolipoprotein ε (APOE4) carriers, while among APOE4 non-carriers BCHE-K appears to be protective. Nonetheless, pure pharmacogenetic reports have provided conflicting results. To provide insights about these controversies, we combined BCHE-K pharmacogenetic observations in AD patients (n = 179) with proteomic and enzymatic analysis of plasma, cerebrospinal fluid (CSF), or both samples. We found that BCHE-K genotype was overrepresented among the AD patients (χ(2) = 14.21, p < 0.0001). Plasma BuChE activity was gene dose-dependently 20-50% less among K-carriers (p < 0.001). CSF BuChE activity did not show such robust K-gene dosage-dependency, because K homozygotes (n = 9) had 30-40% less activity compared to both non-carriers (n = 78, p < 0.01) and heterozygotes (n = 42, p < 0.09). CSF ApoE protein expression was also altered by presence of K-allele (p < 0.001, n = 129). Mutually, APOE4 altered phenotypic display of BuChE variants in CSF (p < 0.01, n = 129). In absence of APOE4, CSF BuChE activity was essentially indistinguishable among K-carriers (n = 16) and non-carriers (n = 17, p < 0.8) although the K-carriers had 24-39% less circulating BuChE protein. In contrast in presence of APOE4, the K-carriers (n = 35) had K allele dose-dependently a BuChE phenotype with 14-46% reduced activity compared to K non-carriers (p < 0.001, n = 59), despite an essentially identical BChE concentration in CSF (1 ± 4%, p < 0.8). Pattern of the patients' cognitive performance in MMSE closely resembled the APOE4-derived phenotypic display of BuChE variants. APOE4-dependent outcome of BCHE-K genotype as AD risk factor arises through a differential phenotypic modulation of BuChE. Future pharmacogenetic studies should include assessment of the subjects' true phenotypic display of BuChE.
Dacron or ePTFE for femoro-popliteal above-knee bypass grafting: short- and long-term results of a multicentre randomised trial.

To compare expanded polytetrafluoroethylene (ePTFE) prosthesis and collagen-impregnated knitted polyester (Dacron) for above-knee (AK) femoro-popliteal bypass grafts.



A prospective multicentre randomised clinical trial.



Between 1992 and 1996, 228 AK femoro-popliteal bypass grafts were randomly allocated to either an ePTFE (n=114) or a Dacron (n=114) vascular graft (6mm in diameter). Patients were eligible for inclusion if presenting with disabling claudication, rest pain or tissue loss. Follow-up was performed and included clinical examination and duplex ultrasonography at all scheduled intervals. All patients were treated with warfarin. The main end-point of this study was primary patency of the bypass graft at 2, 5 and 10 years after implantation. Secondary end-points were mortality, primary assisted patency and secondary patency. Cumulative patency rates were calculated with life-table analysis and with log-rank test.



After 5 years, the primary, primary assisted and secondary patency rates were 36% (confidence interval (CI): 26-46%), 46% (CI: 36-56%) and 51% (CI: 41-61%) for ePTFE and 52% (CI: 42-62%) (p=0.04), 66% (CI: 56-76%) (p=0.01) and 70% (CI: 60-80%) (p=0.01) for Dacron, respectively. After ten years these rates were respectively 28% (CI:18-38%), 31% (CI:19-43%) and 35% (CI: 23-47%) for ePTFE and 28% (CI: 18-38%), 49% (CI: 37-61%) and 49% (CI: 37-61%) for Dacron.



During prolonged follow-up (10 years), Dacron femoro-popliteal bypass grafts have superior patency compared to those of ePTFE grafts. Dacron is the graft material of choice if the saphenous vein is not available.
The influence of transcutaneous electrical neurostimulation (TENS) on human cerebral blood flow velocities

It has been shown that transcutaneous electrical neurostimulation (TENS) reduces sympathetic tone. Spinal cord stimulation (SCS) has proven qualities to improve coronary, peripheral, and cerebral blood circulation. Therefore, we postulate that TENS and SCS affect the autonomic nervous system in analogous ways. In this line of thought, cervical application of TENS might be a useful and simple adjunct in the treatment of cerebrovascular disease by improving cerebral blood flow. Experiments were performed in order to assess whether cervical TENS is safe and whether an effect on cerebral blood flow velocity (CBFV) can be shown in healthy subjects. A controlled, non-randomized, phase 1 study was performed with 20 healthy volunteers. Cervical TENS was applied in several frequencies, with and without hyperventilation. Continuous registration of blood pressure, pulse, CBFV (estimated by transcranial Doppler sonography) and end-tidal carbon dioxide concentration was performed. Cervical TENS was well-tolerated by all subjects. Despite small effects on heart rate (HR) and mean arterial blood pressure (MAP), a significant effect on middle cerebral artery (MCA) blood flow velocity was not demonstrated. No effect of age, gender, current or session order on MCA, HR, or MAP was found. TENS did not influence the effect of hyperventilation. In these experiments, application of cervical TENS is proven to be a safe procedure. However, no effects on cerebral blood flow velocity could be detected, perhaps due to the intact cerebral autoregulation in the healthy volunteers.
Pre-treatment with Irbesartan attenuates left atrial stunning after electrical cardioversion of atrial fibrillation.

Left atrial (LA) stunning, the transient impairment of LA function, is responsible for an increased thrombo-embolic risk after cardioversion of atrial fibrillation (AF). Angiotensin receptor blockers (ARBs) attenuate atrial remodelling in AF and could theoretically influence LA stunning. We studied the effect of Irbesartan on LA stunning.



We prospectively assigned 50 patients from the outpatient clinic undergoing electrical cardioversion for AF with duration of >4 weeks, into two matched groups: 25 patients were treated with Irbesartan (228+/-93 mg/day) for at least 2 weeks prior to cardioversion (Irbesartan group); 25 patients did not receive ARBs (control group). The groups did not differ concerning age (64+/-13 vs. 63+/-13 years, respectively), AF duration (20+/-18 vs. 20+/-19 weeks), underlying disease, LA diameter (46+/-7 vs. 47+/-9 mm), left ventricular dimensions, and ejection fraction (47.7+/-11.6 vs. 49.7+/-14.5%). We assessed LA appendage emptying velocities (LAAEV) and LA spontaneous echo contrast (LASEC) by transoesophageal echocardiography before and after cardioversion and at 2 weeks, and the A-wave by transthoracic echocardiography after cardioversion, at 2 and at 4 weeks. LA stunning was significantly attenuated in the Irbesartan group. The reduction of LAAEV immediately after cardioversion was significantly less in the Irbesartan group (LAAEV reduction of 9+/-49% from 28+/-9 cm/s before cardioversion to 25+/-13 cm/s immediately afterwards) than in the control group (reduction of 48+/-20% from 34+/-15 cm/s before cardioversion to 16+/-6 cm/s afterwards) (P = 0.048). New or increased LASEC occurred in eight patients (32%) in the Irbesartan vs. 16 patients (64%) in the control group (P = 0.046).



Irbesartan significantly attenuates LA stunning after electrical cardioversion of AF. Therefore, ARBs may represent an important pharmacological supplementation in patients being prepared for cardioversion.
Pharmacokinetics of afatinib, a selective irreversible ErbB family blocker, in patients with advanced solid tumours.

Afatinib is a potent, irreversible, ErbB family blocker in clinical development for the treatment of a variety of solid tumours. This study evaluated the pharmacokinetics of afatinib (10-100 mg once daily) in cancer patients.



Data from 221 patients with advanced solid tumours in four phase I and one phase II trial were analysed using non-compartmental methods.



Within each dose group, the shape of the geometric mean plasma concentration-time profiles after single and multiple doses were comparable. Maximum plasma concentration (C(max)) values were achieved 2-5 h after dosing and thereafter declined at least bi-exponentially. Steady-state plasma concentrations were attained within 8 days after the start of dosing. The geometric mean terminal elimination half-life at steady state was about 37 h. Repeated dosing resulted in a 2.77-fold accumulation based on the area under the plasma concentration-time curve (AUC), and 2.11-fold accumulation based on C(max) values. A slightly more than dose-proportional increase in afatinib exposure was observed. There was moderate intra-individual variability in afatinib trough concentration values (the geometric coefficient of variation (gCV) ranged from 22.2 to 67.5 %). The inter-patient variability in plasma concentrations was moderate to high (e.g. at the 40 mg dose, the gCVs ranged from 35.6 to 221 %). The exposure to afatinib (as measured by AUC and C(max)) correlated with the severity of the most common adverse events of afatinib--diarrhoea and rash.



The pharmacokinetic profile of afatinib supports a once-daily dosage regimen. As expected for this patient population, the pharmacokinetic parameters of afatinib showed moderate to high inter-patient variability. Afatinib exhibits non-linear pharmacokinetics.
Psychosocial and cardiac outcomes of yoga for ICD patients: a randomized clinical control trial.

Because as many as 46% of implantable cardioverter defibrillator (ICD) patients experience clinical symptoms of shock anxiety, this randomized controlled study evaluated the efficacy of adapted yoga (vs usual care) in reducing clinical psychosocial risks shown to impact morbidity and mortality in ICD recipients.



Forty-six participants were randomized to a control group or an 8-week adapted yoga group that followed a standardized protocol with weekly classes and home practice. Medical and psychosocial data were collected at baseline and follow-up, then compared and analyzed.



Total shock anxiety decreased for the yoga group and increased for the control group, t(4.43, 36), P < 0.0001, with significant differences between these changes. Similarly, consequential anxiety decreased for the yoga group but increased for the control group t(2.86,36) P = 0.007. Compared to the control, the yoga group had greater overall self-compassion, t(-2.84,37), P = 0.007, and greater mindfulness, t(-2.10,37) P = 0.04, at the end of the study. Exploratory analyses utilizing a linear model (R(2) = 0.98) of observed device-treated ventricular (DTV) events revealed that the expected number of DTV events in the yoga group was significantly lower than in the control group (P < 0.0001). Compared to the control, the yoga group had a 32% lower risk of experiencing device-related firings at end of follow-up.



Our study demonstrated psychosocial benefits from a program of adapted yoga (vs usual care) for ICD recipients. These data support continued research to better understand the role of complementary medicine to address ICD-specific stress in cardiac outcomes.
Diagnostic accuracy of a 2D left ventricle hypertrophy score for familial hypertrophic cardiomyopathy.

To study the diagnostic value of a new 2D left ventricle hypertrophy (2D LVH) score in families with hypertrophic cardiomyopathy (HCM) in comparison with the conventional maximal wall thickness (MWT) measurement (>13 mm in adults), which is limited by a low sensitivity in relatives.



The study was performed in 237 adults from genotyped families with HCM.  A (derivation sample) comprised 109 adults and population B (validation sample) comprised 128 adults. MWT and 2D LVH scores (sum of thicknesses of four segments) were determined by echocardiography. Genotyping was the gold standard for diagnosis. In population A, a theoretical value for LVH score was determined in the healthy population by a multiple linear regression model including age, sex, and body surface area. An abnormal cut-off value was defined as an LVH score above a maximum theoretical value according to receiver operating characteristic analysis. Sensitivity and specificity were, respectively, 73 and 96% for 2D LVH score and 62.5 and 100% for MWT. Improvement of sensitivity was particularly important in adults <50 years of age (69 vs. 54%, respectively, P<0.04). These results were validated in population B: sensitivity and specificity of LVH score were, respectively, 75 and 96% in this sample and 67 and 97%, in the subgroup <50 years. In the latter, sensitivity of LVH score increased when compared with that of MWT (67 vs. 53%, P<0.03).



The LVH score has a higher diagnostic value for HCM than the conventional criterion of MWT, particularly in young adults. This echographic parameter may be proposed as an alternative diagnostic criterion for familial screening.
Short-term outcome of primary operated early breast cancer by hormone and HER-2 receptors

Prognostic subgroup classification of operable breast cancers using cDNA clustering of breast cancer-related genes resembles the classification based on the combined immunohistochemical (IHC) expression of the hormone and HER-2 receptors. We here report the short-term disease-free interval (DFI) of operable breast cancers by their joint hormone receptor/HER-2 phenotype.  Receptors were evaluated using IHC. Steroid receptors were considered positive for any nuclear staining; HER-2 for strong (3+) membrane staining or positive fluorescence in situ hybridization (FISH). Kaplan–Meier (KM) DFI curves were calculated for any relapse defined as a local, regional, contralateral, or distant breast cancer event for the six predefined breast cancer subgroups: ER + PR + HER-2 − (PPN), ER + PR − HER-2 − (PNN), ER + PR + HER-2 + (PPP), ER – PR − HER-2 − (NNN), ER – PR − HER-2 + (NNP), and ER + PR − HER-2 + (PNP). P-values were calculated for comparison of the six different survival curves using two possible adaptations for multiple testing. A multivariate model for the receptors predicting DFI did incorporate local and systemic adjuvant therapy.  Median patient age was 57 years (ranges 26–96) and median FU was 3.35 years. Overall, DFI at median FU was 91%; 94% for PPN, 89% for PNN, 86% for NNN, 81% for PPP, 80% for PNP, and 76% for NNP cases. Some receptor subgroups had a significantly better DFI than others based on multiple testing, especially when the PPN group was compared against the four most frequent subtypes. The multivariate model with local and systemic adjuvant therapy confirmed the prognostic value of ER, PR, and HER-2 for short-term DFI.  It is possible to distinguish short-term prognostic breast cancer subgroups only on the basis of ER, PR, and HER-2 even when stratified for local and systemic adjuvant therapy. While gene expression profiles based on microarray data of over hundreds of genes will probably teach us much about breast cancer biology, heterogeneity, and prognosis, we emphasize the important short-term prognostic value of currently used IHC markers for ER, PR, and HER-2.
Characteristics and associated factors of Klee cartilage lesions: preliminary baseline-data of more than 1000 patients from the German cartilage registry (KnorpelRegister DGOU)

Knee cartilage lesions are very frequent in arthroscopic surgery. This multi-center-study was aimed to evaluate the distribution and possible associated factors of these pathologies in more than 1000 patients. The German cartilage registry (KnorpelRegister DGOU) started in 2013. In this paper, we present the baseline-data (distribution of knee cartilage lesions and the demographic data) of more than 1000 cases since the registries’ start-up. A total number of 47 centers were involved into this multicenter study. A total of 1071 patients primary were registered. Degenerative knees 629 times (61.8 %) and injured knees 302 times (29.6 %) were involved. In the remaining 89 knees (8.7 %) the genesis of cartilage lesions was unclear. Single defects were observed in 792 cases (77.6 %). Most frequently the medial femoral condyle or the patella was affected. In 78 knees (7.6 %) the main-defect was associated with a defect of the corresponding joint surface. In the remaining cases complex cartilage damages were found. Our results are in confirmation with other multicenter studies. But these former studies did not differentiate into traumatic and degenerative lesions. Furthermore no characteristics were given regarding to single, kissing or complex lesions. Thus this database will be a sufficient instrument for the investigation of the “natural course” of cartilage lesions, but above all about the effectiveness of different treatment options.
DE-310, a macromolecular prodrug of the topoisomerase-I-inhibitor exatecan (DX-8951), in patients with operable solid tumors

DE-310 is composed of the topoisomerase-I-inhibitor DX-8951 (exatecan) and a biodegradable macromolecular carrier, which are covalently linked by a peptidyl spacer. In pre-clinical studies, high levels and prolonged retention of conjugated DX-8951 (carrier-bound DX-8951) have been observed in tumor tissues following DE-310 administration. This phenomenon is explained as the enhanced permeability and retention (EPR) effect. DX-8951 and G-DX-8951 (glycyl-DX-8951) exerting anti-tumor activity in vivo are released from DE-310 by enzymatic cleavage of the spacer.  To quantify the concentration of conjugated DX-8951, DX-8951 and G-DX-8951 in human tissues, six patients with different solid tumor types received 6.0 mg/m2 of DE-310 (as equvalent of DX-8951) as a single three-hour infusion administered 7 days (±2 days) prior to scheduled tumor resection. Drug concentrations were then determined in the resected tissues. To evaluate the plasma PK of DE-310, plasma samples were taken up to 42 days post dosing.  There were no severe side effects of the DE-310 infusion. Concentrations of conjugated DX-8951, DX-8951 and G-DX-8951 were in general similar in tumor and relevant normal tissue samples and preferential accumulation of DE-310, DX-8951 and G-DX-8951 in human tumor tissues was not observed.  These data indicate that there is distribution of DE-310 into tissue and that DX-8951 and G-DX-8951 are released slowly over an extended period from DE-310 providing prolonged exposure similar to a continuous infusion. However, the similarity in the concentrations in tumor and relevant normal tissues does not support the EPR concept in the studied human cancers.