nils-herrmann/clean_scirepeval huggingface dataset:
Induction of HIV-1-specific mucosal immune responses following intramuscular recombinant adenovirus serotype 26 HIV-1 vaccination of humans.

Defining mucosal immune responses and inflammation to candidate human immunodeficiency virus type 1 (HIV-1) vaccines represents a current research priority for the HIV-1 vaccine field. In particular, it is unclear whether intramuscular immunization can elicit immune responses at mucosal surfaces in humans.



In this double-blind, randomized, placebo-controlled clinical trial, we evaluated systemic and mucosal immune responses to a candidate adenovirus serotype 26 (Ad26) vectored HIV-1 envelop (Env) vaccine in baseline Ad26-seronegative and Ad26-seropositive healthy volunteers. Systematic mucosal sampling with rectal Weck-Cel sponges and rectal biopsies were performed.



Intramuscular immunization elicited both systemic and mucosal Env-specific humoral and cellular immune responses in the majority of subjects. Individuals with preexisting Ad26-specific neutralizing antibodies had vaccine-elicited immune responses comparable to those of subjects who were Ad26 seronegative. We also observed no increase in activated total or vector-specific mucosal CD4+ T lymphocytes following vaccination by either histopathology or flow cytometry.



These data demonstrate that a single intramuscular administration of this Ad26-vectored HIV-1 Env vaccine elicited both systemic and mucosal immune responses in humans. Induction of antigen-specific humoral and cellular mucosal immunity was not accompanied by a detectable increase in mucosal inflammation.
CYP2D6 polymorphism in systemic lupus erythematosus patients

To determine whether patients with idiopathic systemic lupus erythematosus (SLE) are associated with impaired CYP2D6 activity and to gain insight into whether there is an association between particular CYP2D6 genotypes and susceptibility to SLE, and whether CYP2D6 polymorphism is linked to any specific clinical features of SLE.  Debrisoquine sulfate (10 mg p.o.) was given to 159 healthy volunteers and 39 idiopathic SLE patients. Genotypic assay was carried out in 80 healthy volunteers and 32 patients. A 10-ml blood sample was drawn for genotypic assay. Debrisoquine and 4-hydroxydebrisoquine were determined in 8-h urine samples. Blood samples were analysed for the presence of mutations in the CYP2D6 gene, by using polymerase chain reaction (PCR) specific for CYP2D6*3 and CYP2D6*4 alleles.  The metabolic ratio of debrisoquine to 4-hydroxydebrisoquine ranged from 0.01 to 86.98 in healthy subjects and from 0.02 to 96 in SLE patients. We observed the poor metabolizer(PM) debrisoquine phenotype in three of 39 patients with idiopathic SLE (7.6%) and five of 159 healthy subjects (3.1%). There was no significant difference in the frequency of PM phenotypes between idiopathic SLE and healthy subjects (Fisher's exact test, P = 0.19). No significant difference in the distribution of overall genotypes and allele frequencies were observed between the two groups. No significant relationships were found between specific clinical features and the overall genotype.  The results of this study confirm that CYP2D6 activity is not impaired in SLE and that there is no association between SLE and phenotypic CYP2D6 status. The results also showed that there was no difference in the frequency of CYP2D6A and CYP2D6B alleles between controls and patients with SLE.
Lansoprazole as a rescue agent in chemoresistant tumors: a phase I/II study in companion animals with spontaneously occurring tumors

The treatment of human cancer has been seriously hampered for decades by resistance to chemotherapeutic drugs. Mechanisms underlying this resistance are far from being entirely known. A very efficient mechanism of tumor resistance to drugs is related to the modification of tumour microenvironment through changes in the extracellular and intracellular pH. The acidification of tumor microenvironment depends on proton pumps that actively pump protons outside the cells, mostly to avoid intracellular acidification. In fact, we have shown in pre-clinical settings as pre-treatment with proton-pumps inhibitors (PPI) increase tumor cell and tumor responsiveness to chemotherapeutics. In this study pet with spontaneously occurring cancer proven refractory to conventional chemotherapy have been recruited in a compassionate study. Thirty-four companion animals (27 dogs and 7 cats) were treated adding to their chemotherapy protocols the pump inhibitor lansoprazole at high dose, as suggested by pre-clinical experiments. Their responses have been compared to those of seventeen pets (10 dogs and 7 cats) whose owners did not pursue any other therapy than continuing the currently ongoing chemotherapy protocols. The drug was overall well tolerated, with only four dogs experiencing side effects due to gastric hypochlorhydria consisting with vomiting and or diarrhea. In terms of overall response twenty-three pets out of 34 had partial or complete responses (67.6%) the remaining patients experienced no response or progressive disease however most owners reported improved quality of life in most of the non responders. On the other hand, only three animals in the control group (17%) experienced short lived partial responses (1-3 months duration) while all the others died of progressive disease within two months. high dose proton pump inhibitors have been shown to induce reversal of tumor chemoresistance as well as improvement of the quality of life in pets with down staged cancer and in the majority of the treated animals PPI were well tolerated. Further studies are warranted to assess the efficacy of this strategy in patients with advanced cancers in companion animals as well as in humans.
Reliability and validity of the C-BiLLT: a new instrument to assess comprehension of spoken language in young children with cerebral palsy and complex communication needs.

In clinical practice, a variety of diagnostic tests are available to assess a child's comprehension of spoken language. However, none of these tests have been designed specifically for use with children who have severe motor impairments and who experience severe difficulty when using speech to communicate. This article describes the process of investigating the reliability and validity of the Computer-Based Instrument for Low Motor Language Testing (C-BiLLT), which was specifically developed to assess spoken Dutch language comprehension in children with cerebral palsy and complex communication needs. The study included 806 children with typical development, and 87 nonspeaking children with cerebral palsy and complex communication needs, and was designed to provide information on the psychometric qualities of the C-BiLLT. The potential utility of the C-BiLLT as a measure of spoken Dutch language comprehension abilities for children with cerebral palsy and complex communication needs is discussed.
Comparison of oral and computerized versions of the word memory test.

A computer-administered version of the Word Memory Test (WMT) was compared with the orally administered version in two clinical samples to assess equivalency of the two versions. The two samples included inpatients at an epilepsy center (n = 67) and forensic and clinical referrals to a private practice (n = 58). A randomized procedure was used to assign participants to either version of the WMT. Only the results of the WMT primary effort measures were analyzed. Between-group comparisons of the WMT effort measures were conducted using Mann-Whitney nonparametric analysis. No significant differences were found between versions for several diagnostic subgroups. The data generally support equivalency of the orally administered version and the computerized version of the WMT effort measures in a mixed outpatient sample.
Chocolate consumption and bone density in older women.

Nutrition is important for the development and maintenance of bone structure and for the prevention of osteoporosis and fracture. The relation of chocolate intake with bone has yet to be investigated.



We investigated the relation of chocolate consumption with measurements of whole-body and regional bone density and strength.



Randomly selected women aged 70-85 y (n=1460) were recruited from the general population to a randomized controlled trial of calcium supplementation and fracture risk. We present here a cross-sectional analysis of 1001 of these women. Bone density and strength were measured with the use of dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, and quantitative ultrasonography. Frequency of chocolate intake was assessed with the use of a questionnaire and condensed into 3 categories: <1 time/wk, 1-6 times/wk, >or=1 time/d.



Higher frequency of chocolate consumption was linearly related to lower bone density and strength (P<0.05). Daily (>or=1 times/d) consumption of chocolate, in comparison to <1 time/wk, was associated with a 3.1% lower whole-body bone density; with similarly lower bone density of the total hip, femoral neck, tibia, and heel; and with lower bone strength in the tibia and the heel (P<0.05, for all). Adjustment for covariates did not influence interpretation of the results.



Older women who consume chocolate daily had lower bone density and strength. Additional cross-sectional and longitudinal studies are needed to confirm these observations. Confirmation of these findings could have important implications for prevention of osteoporotic fracture.
Perfusion deficits detected by arterial spin-labeling in patients with TIA with negative diffusion and vascular imaging.

A substantial portion of clinically diagnosed TIA cases is imaging-negative. The purpose of the current study is to determine if arterial spin-labeling is helpful in detecting perfusion abnormalities in patients presenting clinically with TIA.



Pseudocontinuous arterial spin-labeling with 3D background-suppressed gradient and spin-echo was acquired on 49 patients suspected of TIA within 24 hours of symptom onset. All patients were free of stroke history and had no lesion-specific findings on general MR, DWI, and MRA sequences. The calculated arterial spin-labeling CBF maps were scored from 1-3 on the basis of presence and severity of perfusion disturbance by 3 independent observers blinded to patient history. An age-matched cohort of 36 patients diagnosed with no cerebrovascular events was evaluated as a control. Interobserver agreement was assessed by use of the Kendall concordance test.



Scoring of perfusion abnormalities on arterial spin-labeling scans of the TIA cohort was highly concordant among the 3 observers (W = 0.812). The sensitivity and specificity of arterial spin-labeling in the diagnosis of perfusion abnormalities in TIA was 55.8% and 90.7%, respectively. In 93.3% (70/75) of the arterial spin-labeling CBF map readings with positive scores (≥2), the brain regions where perfusion abnormalities were identified by 3 observers matched with the neurologic deficits at TIA onset.



In this preliminary study, arterial spin-labeling showed promise in the detection of perfusion abnormalities that correlated with clinically diagnosed TIA in patients with otherwise normal neuroimaging results.
Clinical trials in acute myocardial infarction: should we adjust for baseline characteristics?

Clinical trials concerning acute myocardial infarction often evaluate short-term death. Several baseline characteristics are predictors of death, most notably age. Adjustment for one or more predictors in a multivariable analysis may be considered to correct the estimate of the treatment effect for any imbalance that by chance may have occurred between the randomized groups. Moreover, adjustment results in a stratified estimate of the effect of treatment.



The effects of adjustment (correction for imbalance and stratification) were studied with logistic regression analysis in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO)-I trial. The primary end point was 30-day death, which occurred in 6.3% of 10,348 patients randomly assigned to tissue plasminogen activator and 7.3% of 20,162 patients randomly assigned to streptokinase thrombolytic therapy. This is equivalent to an unadjusted odds ratio of 0.853. No significant imbalance had occurred for any of 17 baseline characteristics considered, including well-known demographic, presenting, and history characteristics. Adjusted for age, the odds ratio was 0.829, which is an 18% increase in estimated effect on the logistic scale. When adjusted for 17 characteristics, the odds ratio was 0.820, an increase of 25%. The increase in effect estimate was largely explained by the stratification effect and only partly by imbalance of predictors.



Adjustment for predictive baseline characteristics, even when largely balanced, may lead to clearly different estimates of the treatment effect on mortality rates. Adjustment for important predictors such as age is recommended in clinical trials studying patients with acute myocardial infarction.
Implementing multidestination worms in switch-based parallel systems: architectural alternatives and their impact

Multidestination message passing has been proposed as an attractive mechanism for efficiently implementing multicast and other collective operations on direct networks. However, applying this mechanism to switch-based parallel systems is non-trivial. In this paper we propose alternative switch architectures with differing buffer organizations to implement multidestination worms on switch-based parallel systems. First, we discuss issues related to such implementation (deadlock-freedom, replication mechanisms, header encoding, and routing). Next, we demonstrate how an existing central-buffer-based switch architecture supporting unicast message passing can be enhanced to accommodate multidestination message passing. Similarly, implementing multidestination worms on an input-buffer-based switch architecture is discussed. Both of these implementations are evaluated against each other as well as against a software-based scheme using the central buffer organization. Simulation experiments under a range of traffic (multiple multicast, bimodal, varying degree of multicast, and message length) and system size are used for evaluation. The study demonstrates the superiority of the central-buffer-based switch architecture. It also indicates that under bimodal traffic the central-buffer-based hardware multicast implementation affects background unicast traffic less adversely compared to a software-based multicast implementation. Thus, multidestination message passing can easily be applied to switch-based parallel systems to deliver good collective communication performance.
Reducing control overhead in dataflow architectures

In recent years, computer architects have proposed tiled architectures in response to several emerging problems in processor design, such as design complexity, wire delay, and fabrication reliability. One of these architectures, WaveScalar, uses a dynamic, tagged-token dataflow execution model to simplify the design of the processor tiles and their interconnection network and to achieve good parallel performance. However, using a dataflow execution model reawakens old problems, including the instruction overhead required for control flow. Previous work compiling the functional language Id to the Monsoon Dataflow System found this overhead to be 2–3× that of programs written in C and targeted to a MIPS R3000.In this paper, we present and analyze three compiler optimizations that significantly reduce control overhead with minimal additional hardware. We begin by describing how to translate imperative code into dataflow assembly and analyze the resulting control overhead. We report a similar 2–4× instruction overhead, which suggests that the execution model, rather than a specific source language or target architecture, is responsible. Then, we present the compiler optimizations, each of which is designed to eliminate a particular type of control overhead, and analyze the extent to which they were able to do so. Finally, we evaluate the effect using all optimizations together has on program performance. Together, the optimizations reduce control overhead by 80% on average, increasing application performance between 21–37%.
Meta-Analyses of Microarray Datasets Identifies ANO1 and FADD as Prognostic Markers of Head and Neck Cancer

The head and neck squamous cell carcinoma (HNSCC) transcriptome has been profiled extensively, nevertheless, identifying biomarkers that are clinically relevant and thereby with translational benefit, has been a major challenge. The objective of this study was to use a meta-analysis based approach to catalog candidate biomarkers with high potential for clinical application in HNSCC. Data from publically available microarray series (N = 20) profiled using Agilent (4X44K G4112F) and Affymetrix (HGU133A, U133A_2, U133Plus 2) platforms was downloaded and analyzed in a platform/chip-specific manner (GeneSpring software v12.5, Agilent, USA). Principal Component Analysis (PCA) and clustering analysis was carried out iteratively for segregating outliers; 140 normal and 277 tumor samples from 15 series were included in the final analysis. The analyses identified 181 differentially expressed, concordant and statistically significant genes; STRING analysis revealed interactions between 122 of them, with two major gene clusters connected by multiple nodes (MYC, FOS and HSPA4). Validation in the HNSCC-specific database (N = 528) in The Cancer Genome Atlas (TCGA) identified a panel (ECT2, ANO1, TP63, FADD, EXT1, NCBP2) that was altered in 30% of the samples. Validation in treatment naïve (Group I; N = 12) and post treatment (Group II; N = 12) patients identified 8 genes significantly associated with the disease (Area under curve>0.6). Correlation with recurrence/re-recurrence showed ANO1 had highest efficacy (sensitivity: 0.8, specificity: 0.6) to predict failure in Group I. UBE2V2, PLAC8, FADD and TTK showed high sensitivity (1.00) in Group I while UBE2V2 and CRYM were highly sensitive (>0.8) in predicting re-recurrence in Group II. Further, TCGA analysis showed that ANO1 and FADD, located at 11q13, were co-expressed at transcript level and significantly associated with overall and disease-free survival (p<0.05). The meta-analysis approach adopted in this study has identified candidate markers correlated with disease outcome in HNSCC; further validation in a larger cohort of patients will establish their clinical relevance.
Role of reticulated platelets and platelet size heterogeneity on platelet activity after dual antiplatelet therapy with aspirin and clopidogrel in patients with stable coronary artery disease.

The aim of this study was to evaluate the relationship between reticulated platelets (RPs), platelet size, and platelet function in patients with stable coronary artery disease (CAD) taking aspirin and clopidogrel.



Reticulated platelets are young platelets that are larger and possibly more active than non-RPs.



Flow cytometry was used to measure RPs after staining with thiazole orange and to define the upper 20% and lower 20% of platelets by size. Platelet aggregation was measured with light transmission aggregometry (LTA); platelet activation was assessed by measuring activated platelet surface expression of P-selectin and glycoprotein (GP) IIb/IIIa.



Ninety patients were recruited and stratified into tertiles of %RPs. Patients in the upper tertile displayed greater platelet aggregation to 5-mumol/l adenosine diphosphate (ADP) (50.7 +/- 16.4% vs. 34.2 +/- 17.3%, p < 0.001), 1.5-mmol/l arachidonic acid (AA) (27.3 +/- 16.9% vs. 11.7 +/- 9.3%, p < 0.001), and 1-mug/ml collagen (18 +/- 11.6% vs. 12.1 +/- 8.7%, p < 0.05) and greater expression of GP IIb/IIIa (4.7 +/- 1.8% vs. 3.1 +/- 2.2%, p < 0.001). Frequency of low response to aspirin (AA LTA >20%) was higher in the upper tertile (53% vs. 17%, p < 0.001) compared with the lower tertile; low response to clopidogrel (ADP LTA >50%) was also elevated in the upper tertile (50% vs. 13%, p = 0.003). The larger platelet gate had a higher % of RPs compared with the smaller gate (15.4 +/- 16.7% vs. 1.7 +/- 2.3%, p < 0.001) and greater GP IIb/IIIa (5.7 +/- 3.1 vs. 2.1 +/- 1.2, p < 0.001) and P-selectin expression (7.8 +/- 4.9 vs. 4.6 +/- 2.7, p < 0.001).



The proportion of circulating RPs strongly correlates with response to antiplatelet therapy in patients with stable CAD. Large platelets exhibit increased reactivity despite dual antiplatelet therapy, compared with smaller platelets.
Association between GSK3β gene and increased impulsivity in bipolar disorder

Bipolar patients present increased levels of impulsivity even during remission periods. It is known that this dimensional trait negatively impacts on the course of illness and worsens their prognosis and outcome. Evidence from both basic and clinical researches supports that Lithium (Li) may decrease impulsivity. Owing to the fact that Li inhibits both glycogen synthetase kinase-3 (GSK3) isoenzimes, our aim was to analyze the potential impact of genetic variants located at the GSK3 α and β genes on impulsivity levels in a bipolar sample. Our sample consisted of 199 unrelated Caucasian bipolar outpatients who were recruited from the Bipolar Disorder Unit of the Hospital Clinic of Barcelona and from primary care settings from Oviedo. Four polymorphisms at the GSK3 α and β genes were genotyped in order to analyze the impact of genetic variability on impulsivity as measured by the BIS-11 scale. Single SNP analysis showed that patients carrying T and G alleles at the rs1732170-GSK3β and the rs334558-GSK3β, respectively, presented increased levels of attentional impulsivity compared to non-carriers. These results were also confirmed by haplotype analysis. Our results suggest that genetic variability at GSK3β gene is associated to increased impulsivity in bipolar patients.
A first-in-class, first-in-human, phase I trial of p28, a non-HDM2-mediated peptide inhibitor of p53 ubiquitination in patients with advanced solid tumours

This first-in-human, phase I clinical trial of p28 (NSC745104), a 28-amino-acid fragment of the cupredoxin azurin, investigated the safety, tolerability, pharmacokinetics and preliminary activity of p28 in patients with p53+ metastatic solid tumours.A total of 15 patients were administered p28 i.v. as a short infusion three times per week for 4 weeks followed by a 2-week rest under an accelerated titration 3+3 dose escalation design until either a grade 3-related adverse event occurred or the maximum tolerated dose (MTD) was reached. Single-dose and steady-state serum pharmacokinetics were characterised. Assessments included toxicity, best objective response by RECIST 1.1 Criteria, and overall survival.No patients exhibited any dose-limiting toxicities (DLTs), significant adverse events or exhibited an immune response (IgG) to the peptide. The No Observed Adverse Effect Level (NOAEL) and MTD were not reached. Seven patients demonstrated stable disease for 7–61 weeks, three a partial response for 44–125 weeks, and one a complete response for 139 weeks. Three patients are still alive at 158, 140, and 110 weeks post therapy completion.p28 was tolerated with no significant adverse events. An MTD was not reached. Evidence of anti-tumour activity indicates a highly favourable therapeutic index and demonstrates proof of concept for this new class of non-HDM2-mediated peptide inhibitors of p53 ubiquitination.
A novel kernel method for clustering

Kernel methods are algorithms that, by replacing the inner product with an appropriate positive definite function, implicitly perform a nonlinear mapping of the input data into a high-dimensional feature space. In this paper, we present a kernel method for clustering inspired by the classical k-means algorithm in which each cluster is iteratively refined using a one-class support vector machine. Our method, which can be easily implemented, compares favorably with respect to popular clustering algorithms, like k-means, neural gas, and self-organizing maps, on a synthetic data set and three UCI real data benchmarks (IRIS data, Wisconsin breast cancer database, Spam database).