nils-herrmann/clean_scirepeval huggingface dataset:
Hepatitis C virus genotype and subtype distribution in Chinese chronic hepatitis C patients: nationwide spread of HCV genotypes 3 and 6

Hepatitis C virus (HCV) genotype and subtype are related to disease progression and response to antiviral therapy. Current HCV genotype and subtype distribution data, especially for genotypes 3 and 6, are limited in China. Our purpose was to investigate the current HCV genotype and subtype distributions in chronic hepatitis C patients in China. Chronic hepatitis C patients (n = 1012) were enrolled, and demographic information and possible transmission risk factors were collected. Serum samples were subjected to reverse-transcription polymerase chain reaction, followed by direct DNA sequencing and phylogenetic analysis of the NS5B and core/E1 regions to determine HCV genotypes/subtypes. The geographical distributions of HCV genotypes/subtypes were analyzed. Demographic information and transmission risk factors were compared between different HCV genotypes/subtypes. Four genotypes and seven subtypes of HCV were detected in 970 patients. Subtypes 1b, 2a, 3a, 6a, 3b, 6n, and 1a were detected at frequencies of 71.96 %, 19.90 %, 3.20 %, 2.16 %, 1.96 %, 0.41 %, and 0.41 %, respectively. Genotypes 3 and 6 showed an increasingly wide geographic distribution over time. Patients with subtypes 1b and 2a were older than those with 3a, 3b, 6a, and 6n subtypes (p < 0.05 in all subtypes). More genotype 1 and 2 patients underwent blood transfusion than those with genotype 3 (all p < 0.05). More genotype 3 and 6 patients had a history of intravenous drug use than those with genotypes 1 and 2 (all p < 0.05). Though subtypes 1b and 2a are still the most prevalent HCV subtypes in China, genotype 3 and 6 HCV infections have already spread nationwide from southern and western China.
Cancer and the threat of death: the cognitive dynamics of death-thought suppression and its impact on behavioral health intentions.

Five studies examined the cognitive association between thoughts of cancer and thoughts of death and their implication for screening intentions. Study 1 found that explicit contemplation of cancer did not increase death-thought accessibility. In support of the hypothesis that this reflects suppression of death-related thoughts, Study 2 found that individuals who thought about cancer exhibited elevated death-thought accessibility under high cognitive load, and Study 3 demonstrated that subliminal primes of the word cancer led to increased death-thought accessibility. Study 4 revealed lower levels of death-thought accessibility when perceived vulnerability to cancer was high, once again suggesting suppression of death-related thoughts in response to conscious threats associated with cancer. Study 5 extended the analysis by finding that after cancer salience, high cognitive load, which presumably disrupts suppression of the association between cancer and death, decreased cancer-related self-exam intentions. Theoretical and practical implications for understanding terror management, priming and suppression, and responses to cancer are discussed.
The influence of depression and anxiety symptoms on health-related quality of life in patients with atrial fibrillation and atrial flutter.

The health-related quality of life (HRQoL) of patients with atrial fibrillation (AF) and atrial flutter (AFL) is an important issue in cardiovascular health management. Determinants of poor HRQoL of AF/AFL patients require further elucidation.



The purpose of this study was to evaluate the influencing factors related to the HRQoL of AF/AFL patients.



In 150 consecutively recruited patients in a multicenter, cross-sectional study from April 2010 to February 2011, depression and anxiety were measured with the Beck Depression Inventory II and the State Trait Anxiety Inventory, respectively, whereas HRQoL was assessed with the generic Medical Outcomes Survey 36-Item Short-Form Survey version 2 and the Symptom Checklist. Linear regression modeling was performed to determine predictors of HRQoL among variables, including the patients' age, gender, race, marital status, type of AF/AFL, frequency of AF/AFL symptoms, time since diagnosis, and anxiety and depression symptoms.



Female patients with AF/AFL reported poorer physical HRQoL than male patients did (P < .001, R² = 0.391). Symptoms of depression and anxiety were found to be associated with poorer HRQoL (P < .001, R² = 0.482). Anxiety was the strongest predictor of the mental component of the Medical Outcomes Survey 36-Item Short-Form Survey version 2 and the Symptom Checklist. Younger patients had worse AF/AFL-related symptoms and severity than older patients did (P < .001, R² = 0.302). Increased frequency of symptomatic episodes was associated with worse AF/AFL-related symptoms and severity.



In conclusion, depression and anxiety symptoms and female gender emerged as clear indicators of poor HRQoL in AF/AFL patients. These risk factors should be used to identify patients who may require additional evaluation and treatment efforts to manage their cardiac conditions or HRQoL. Interventions to improve HRQoL in these individuals require further investigation.
Oral Administration of OKT3 MAb to Patients with NASH, Promotes Regulatory T-cell Induction, and Alleviates Insulin Resistance: Results of a Phase IIa Blinded Placebo-Controlled Trial

Oral administration of anti-CD3 antibodies induced regulatory T cells (Tregs) alleviating the insulin resistance and liver damage in animal models. To determine the safety and biological effects of oral OKT3 monoclonal antibody (Balashov et al. Neurology 55:192–8, 2000) in patients with NASH. In this Phase-IIa trial, four groups of patients with biopsy-proven NASH (n = 9/group) received placebo (group A) or oral OKT3 (group B: 0.2; C: 1.0; D: 5.0 mg/day) for 30 days. Patients were followed for safety, liver enzymes, glucose, lipid profile, oral glucose tolerance test (OGTT), serum cytokines and Tregs. Oral OKT3 was well tolerated without treatment-related adverse events. OKT3 induced Tregs: with significant increases of CD4+LAP+ (Latency associated peptide) and CD4+CD25+LAP+ cells in Group D, and a significant increase in TGF-β in Groups C and D. AST decreased significantly in group D and a trend in Groups B and C. Fasting plasma glucose decreased significantly in all treatment groups compared with placebo. OGTT decreased significantly in Group D. Correlations were observed between the changes in several immune-modulatory effects and clinical biomarkers. While serum anti-CD3 levels where undetectable increases in human anti-mouse antibody levels were observed in Groups C and D. Oral administration of anti-CD3 MAb to patients with NASH was safe and well tolerated. Positive biological effects were noted in several hepatic, metabolic and immunologic parameters. These findings provide the basis for future trials to investigate the effect of oral anti-CD3 MAb immunotherapy in patients with NASH.
Aceclofenac in rheumatoid arthritis: A useful and novel anti-inflammatory

The efficacy and safety of 100 mg aceclofenac twice daily was investigated in 73 patients with active rheumatoid arthritis in a multi-centre, double blind, randomised, parallel group, placebo controlled study over a period of 4 weeks. Treatment with aceclofenac was effective in improving the Ritchie articular index (predetermined primary end point), duration of morning stiffness, joint swelling, ARA functional class, patient's and physician's global assessments, and pain. All these improved to a significantly (P<0.05) greater extent than in placebo-treated patients. Grip strength showed a significant improvement from baseline in the aceclofenac-treated group and this was greater than the improvement measured in placebo treated patients. No significant difference was detected between the treatment groups for the number of subjects reporting an adverse event. Aceclofenac administered orally at 100 mg twice daily for four weeks thus produced significant improvements in patients with active rheumatoid arthritis. This treatment was well tolerated with an adverse event profile similar to that of placebo.
Spreading depolarisations and outcome after traumatic brain injury: a prospective observational study

Pathological waves of spreading mass neuronal depolarisation arise repeatedly in injured, but potentially salvageable, grey matter in 50-60% of patients after traumatic brain injury (TBI). We aimed to ascertain whether spreading depolarisations are independently associated with unfavourable neurological outcome.



We did a prospective, observational, multicentre study at seven neurological centres. We enrolled 109 adults who needed neurosurgery for acute TBI. Spreading depolarisations were monitored by electrocorticography during intensive care and were classified as cortical spreading depression (CSD) if they took place in spontaneously active cortex or as isoelectric spreading depolarisation (ISD) if they took place in isoelectric cortex. Investigators who treated patients and assessed outcome were masked to electrocorticographic results. Scores on the extended Glasgow outcome scale at 6 months were fitted to a multivariate model by ordinal regression. Prognostic score (based on variables at admission, as validated by the IMPACT studies) and spreading depolarisation category (none, CSD only, or at least one ISD) were assessed as outcome predictors.



Six individuals were excluded because of poor-quality electrocorticography. A total of 1328 spreading depolarisations arose in 58 (56%) patients. In 38 participants, all spreading depolarisations were classified as CSD; 20 patients had at least one ISD. By multivariate analysis, both prognostic score (p=0·0009) and spreading depolarisation category (p=0·0008) were significant predictors of neurological outcome. CSD and ISD were associated with an increased risk of unfavourable outcome (common odds ratios 1·56 [95% CI 0·72-3·37] and 7·58 [2·64-21·8], respectively). Addition of depolarisation category to the regression model increased the proportion of variance in outcome that could be attributed to predictors from 9% to 22%, compared with the prognostic score alone.



Spreading depolarisations were associated with unfavourable outcome, after controlling for conventional prognostic variables. The possibility that spreading depolarisations have adverse effects on the traumatically injured brain, and therefore might be a target in the treatment of TBI, deserves further research.
AID induces intraclonal diversity and genomic damage in CD86+ chronic lymphocytic leukemia cells

The activation-induced cytidine deaminase (AID) mediates somatic hypermutation and class switch recombination of the Ig genes by directly deaminating cytosines to uracils. As AID causes a substantial amount of off-target mutations, its activity has been associated with lymphomagenesis and clonal evolution of B-cell malignancies. Although it has been shown that AID is expressed in B-cell chronic lymphocytic leukemia (CLL), a clear analysis of in vivo AID activity in this B-cell malignancy remained elusive. In this study performed on primary human CLL samples, we report that, despite the presence of a dominant VDJ heavy chain region, a substantial intraclonal diversity was observed at VDJ as well as at IgM switch regions (Sμ), showing ongoing AID activity in vivo during disease progression. This AID-mediated heterogeneity was higher in CLL subclones expressing CD86, which we identified as the proliferative CLL fraction. Finally, CD86 expression correlated with shortened time to first treatment and increased γ-H2AX focus formation. Our data demonstrate that AID is active in CLL in vivo and thus, AID likely contributes to clonal evolution of CLL.
ETAHM: An energy-aware task allocation algorithm for heterogeneous multiprocessor

In demand of more computing power and less energy use, multiprocessor with power management facility emerges in embedded system design recently. Dynamic Voltage Scaling is such a facility that varies clock speed and supply voltage to save more energy. In this paper, we propose ETAHM to allocate tasks on a target multiprocessor system. In pursuit of global optimal solution, it mixes task scheduling, mapping and DVS utilization in one phase and couples ant colony optimization algorithm. Extensive experiments show ETAHM could save 22.71% more energy than CASPER , a state-of-the-art integrated framework that tackles the identical problem with genetic algorithm instead.
Effects of seated double-poling ergometer training on aerobic and mechanical power in individuals with spinal cord injury.

To determine whether regular interval training on a seated double-poling ergometer can increase physical capacity and safely improve performance towards maximal level in individuals with spinal cord injury.



A total of 13 subjects with spinal cord injury (injury levels T5-L1) performed 30 sessions of seated double-poling ergometer training over a period of 10 weeks. Sub-maximal and maximal double-poling ergometer tests were performed before (test-retest) and after this training period. Oxygen uptake was measured using the Douglas Bag system. Three-dimensional kinematics were recorded using an optoelectronic system and piezoelectric force sensors were used to register force in both poles.



The mean intra-class correlation coefficient for test-retest values was 0.83 (standard deviation 0.11). After training significant improvements were observed in people with spinal cord injury in oxygen uptake (22.7%), ventilation (20.7%) and blood lactate level (22.0%) during maximal exertion exercises. Mean power per stroke and peak pole force increased by 15.4% and 23.7%, respectively. At sub-maximal level, significantly lower values were observed in ventilation (-12.8%) and blood lactate level (-25.0%).



Regular interval training on the seated double-poling ergometer was effective for individuals with spinal cord injury below T5 level in terms of improving aerobic capacity and upper-body power output. The training was safe and did not cause any overload symptoms.
Design and rationale of the GAUSS-2 study trial: a double-blind, ezetimibe-controlled phase 3 study of the efficacy and tolerability of evolocumab (AMG 145) in subjects with hypercholesterolemia who are intolerant of statin therapy.

Statins effectively lower low-density lipoprotein cholesterol (LDL-C), reducing cardiovascular morbidity and mortality. Most patients tolerate statins well, but approximately 10% to 20% experience side effects (primarily muscle-related) contributing to diminished compliance or discontinuation of statin therapy and subsequent increase in cardiovascular risk. Statin-intolerant patients require more effective therapies for lowering LDL-C. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a compelling target for LDL-C-lowering therapy. Evolocumab (AMG 145) is a fully human monoclonal antibody that binds PCSK9, inhibiting its interaction with the LDL receptor to preserve LDL-receptor recycling and reduce LDL-C. Phase 2 studies have demonstrated the safety, tolerability, and preliminary efficacy of subcutaneous evolocumab in diverse populations, including statin-intolerant patients. This article describes the rationale and design of the Goal Achievement After Utilizing an anti-PCSK9 Antibody in Statin-Intolerant Subjects 2 (GAUSS-2) trial, a randomized, double-blind, ezetimibe-controlled, multicenter phase 3 study to evaluate the effects of 12 weeks of evolocumab 140 mg every 2 weeks or 420 mg every month in statin-intolerant patients with hypercholesterolemia. Eligible subjects were unable to tolerate effective doses of ≥2 statins because of myalgia, myopathy, myositis, or rhabdomyolysis that resolved with statin discontinuation. The primary objective of the study is to assess the effects of evolocumab on percentage change from baseline in LDL-C. Secondary objectives include evaluation of safety and tolerability, comparison of the effects of evolocumab vs ezetimibe on absolute change from baseline in LDL-C, and percentage changes from baseline in other lipids. Recruitment of approximately 300 subjects was completed in August 2013.
Awareness during cardiopulmonary bypass.

Recently, numerous studies and reports have been made on awareness under different types of general anesthesia. In our study, 56 patients who underwent coronary artery bypass were grouped into three categories according to the type of anesthesia received. This was done to determine whether the incidence of awareness during cardiopulmonary bypass is related to the anesthetic combinations and techniques. Five out of 56 patients (8.9%) had spontaneous recall of what happened during their operations.
Electrical stimulation of the human homolog of the medial superior temporal area induces visual motion blindness.

Despite tremendous advances in neuroscience research, it is still unclear how neuronal representations of sensory information give rise to the contents of our perception. One of the first and also the most compelling pieces of evidence for direct involvement of cortical signals in perception comes from electrical stimulation experiments addressing the middle temporal (MT) area and the medial superior temporal (MST) area: two neighboring extrastriate cortical areas of the monkey brain housing direction-sensitive neurons. Here we have combined fMRI with electrical stimulation in a patient undergoing awake brain surgery, to separately probe the functional significance of the human homologs, i.e., area hMT and hMST, on motion perception. Both the stimulation of hMT and hMST made it impossible for the patient to perceive the global visual motion of moving random dot patterns. Although visual motion blindness was predominantly observed in the contralateral visual field, stimulation of hMST also affected the ipsilateral hemifield. These results suggest that early visual cortex up to the stage of MT is not sufficient for the perception of global visual motion. Rather, visual motion information must be mediated to higher-tier cortical areas, including hMST, to gain access to conscious perception.
Influence of early prehospital thrombolysis on mortality and event-free survival (the Myocardial Infarction Triage and Intervention [MITI] Randomized Trial). MITI Project Investigators.

The Myocardial Infarction Triage and Intervention Trial of prehospital versus hospital administration of thrombolytic therapy markedly reduced hospital treatment times, but the 2 groups had similar outcomes. However, patients treated < 70 minutes from symptom onset had better short-term outcomes. The purpose of this study was to determine the long-term influence of very early thrombolytic treatment for acute myocardial infarction. A total of 360 patients were followed for vital status and cardiac-related hospital admissions over a period of 34 +/- 16 months. Patients enrolled in the trial had symptoms for < or = 6 hours, ST-segment elevation on the prehospital electrocardiogram, and no risk factors for serious bleeding. They received aspirin and recombinant tissue plasminogen activator either before or after hospital arrival. Primary end points in this study included long-term survival and survival free of death or readmission to the hospital for angina, myocardial infarction, congestive heart failure, or revascularization. Two-year survival was 89% for prehospital- and 91% for hospital-treated patients (p = 0.46). Event-free survival at 2 years was 56% and 64% for prehospital- and hospital-treated patients, respectively (p = 0.42). In patients treated < 70 minutes from symptom onset, 2-year survival was 98%, and it was 88% for those treated later (p = 0.12). Two-year event-free survival was 65% for patients treated early and 59% for patients treated later (p = 0.80). In this trial, poorer long-term survival was associated with advanced age, history of congestive heart failure, and coronary artery bypass surgery performed before the index hospitalization, but not with time to treatment.
Impact of haemoglobin and erythropoietin dose changes on mortality: a secondary analysis of results from a randomized anaemia management trial.

Anaemia is a common complication of chronic kidney disease. A number of studies have identified an adverse association between haemoglobin (Hgb) variability and mortality. To date, no study has evaluated the impact of Hgb variability on mortality in the setting of a uniform Hgb target and erythropoiesis-stimulating agents (ESA) dosing strategy.



One hundred and fifty-four haemodialysis (HD) patients from a previous randomized anaemia management study were followed up for up to 6 years. The impact of Hgb variability and ESA dosing parameters on subsequent mortality risk were evaluated.



More rapid rises in Hgb (Hgb deflect(pos)) and ESA dose increases were independently associated with mortality in multivariate analysis, whereas more rapid Hgb declines (Hgb deflect(neg)) and ESA dose decreases were not. Each gram per litre per week increase in Hgb deflect(pos) was associated with an adjusted hazard ratio (HR) of 1.23 (1.03-1.48), while for every 1000-unit increase in ESA dose, the adjusted HR was 1.12 (1.01-1.24). Factors associated with positive Hgb deflections included frequency and magnitude of ESA dose changes, baseline Hgb, patient weight and presence of an HD catheter.



Rapid Hgb rises and greater average Eprex dose increases were independently associated with a higher mortality risk in HD patients after adjustment for baseline Hgb and Eprex dose. A randomized controlled trial evaluating different ESA dosing strategies in response to individual patient ESA responsiveness is needed.
Phase I first-in-human study of TAK-285, a novel investigational dual HER2/EGFR inhibitor, in cancer patients

This phase I first-in-human study was conducted in Japanese patients to investigate the safety, pharmacokinetics (PKs), and determine the maximum tolerated dose (MTD) of oral TAK-285, a novel dual erbB protein kinase inhibitor that specifically targets human epidermal growth factor receptor (EGFR) and HER2.Methods:The TAK-285 dose was escalated until MTD was determined. A second patient cohort received TAK-285 at the MTD for at least 4 weeks.In all, 26 patients received TAK-285 at doses ranging from 50 to 400 mg once daily (q.d.) or twice daily (b.i.d.); 20 patients made up the dose escalation cohort and the remaining 6 patients were the repeated administration cohort. TAK-285 was well tolerated. Dose-limiting toxicities noted in two patients who received 400 mg b.i.d. were grade 3 increases in aminotransferases and grade 3 decreased appetite. Consequently, the MTD was determined to be 300 mg b.i.d. Absorption of TAK-285 was rapid after oral dosing, and plasma exposure at steady-state increased in a dose-proportional fashion for doses ranging from 50 to 300 mg b.i.d. A partial response was observed for one patient with parotid cancer who received 300 mg b.i.d.The toxicity profile and PK properties of oral TAK-285 warrant further evaluation.