nils-herrmann/clean_scirepeval huggingface dataset:
Identification of microRNAs involved in the modulation of pro-angiogenic factors in atherosclerosis by a polyphenol-rich extract from propolis.

New vessel formation plays a critical role in the progression and vulnerability of atherosclerotic lesions. It has been shown that polyphenols from propolis attenuate the progression of atherosclerosis and also exert inhibitory effects on angiogenic factors. However, the mechanisms underlying these effects are not completely understood. Thus, this study aimed to identify microRNAs (miRNAs) involved in the modulation of pro-angiogenic factors in the atherosclerotic plaques of LDL receptor gene knockout mice treated with a polyphenol-rich extract of Chilean propolis. The progression of the atherosclerotic lesions was significantly attenuated in treated mice compared with control mice. Using microarray analysis and a bioinformatic approach, we identified 29 differentially expressed miRNAs. Many of these miRNAs were involved in biological processes associated with angiogenesis, such as the cell cycle, cell migration, cell growth and proliferation. Among them, three miRNAs (miR-181a, miR-106a and miR-20b) were over-expressed and inversely related to the expression of Vegfa (vascular endothelial growth factor A) and Hif1a (hypoxia inducible factor 1 alpha). In addition, VEGF-A protein expression was attenuated in histological sections obtained from the aortic sinuses of treated mice. VEGFA is a key pro-angiogenic factor in atherosclerotic plaques, and Hif1a, which is expressed in the necrotic nucleus of the atheroma, is its main inducer. We found a correlation between the over-expression of miR-181a, miR-106a and miR-20b and their target genes, Hif1a and Vegfa, which is consistent with attenuation of the atherosclerotic lesion. In conclusion, our data analysis provides evidence that the anti-angiogenic effects of polyphenols from Chilean propolis can be modulated by miRNAs, in particular miR-181a, miR-106a and miR-20b.
Fulvestrant 250 mg versus anastrozole for Chinese patients with advanced breast cancer: results of a multicentre, double-blind, randomised phase III trial

Fulvestrant, an oestrogen receptor (ER) antagonist with no known agonist effects, has shown activity in postmenopausal patients with ER-positive advanced breast cancer recurring or progressing following prior endocrine therapy. This double-blind, double-dummy, randomised phase III study (NCT00327769) was designed to compare the efficacy and safety of fulvestrant versus anastrozole in advanced breast cancer of Chinese postmenopausal women whose disease has progressed following prior endocrine treatment. A total of 234 patients were randomised to fulvestrant 250 mg/month (n = 121) or 1 mg/day anastrozole (n = 113), together with matching placebo. The primary endpoint was time to progression (TTP). Secondary endpoints included objective response rate (ORR), duration of response (DoR), clinical benefit rate (CBR) and time to treatment failure (TTF). Baseline characteristics were similar, with the possible exception that a higher number of fulvestrant patients had received two prior chemotherapy regimens. Median TTP was 110 days in the fulvestrant group versus 159 days in the anastrozole group (hazard ratio [HR], 1.314; 95% confidence intervals [CI], 0.948, 1.822; P = 0.101). ORR was 10% in the fulvestrant group and 14% in the anastrozole group. Median DoR from randomisation to progression was 436 days versus 432 days for the fulvestrant and anastrozole groups, respectively. CBR for fulvestrant (36.1%) versus anastrozole (48.2%) was not statistically different between the groups. TTF (110 days versus 147 days for the fulvestrant and anastrozole groups, respectively) was not statistically different between the treatments (HR, 1.307; 95% CI, 0.961, 1.778; P = 0.088). Both treatments were well tolerated, with only two patients treated with fulvestrant and four patients treated with anastrozole withdrawn from study treatment due to adverse events. These data demonstrate that fulvestrant 250 mg and anastrozole were similarly effective and well tolerated in the treatment of postmenopausal Chinese women with advanced breast cancer whose disease had progressed or recurred on prior endocrine treatment.
Is a combination of varenicline and nicotine patch more effective in helping smokers quit than varenicline alone? A randomised controlled trial

Nicotine replacement therapy (NRT) and varenicline are both effective in helping smokers quit. There is growing interest in combining the two treatments to improve treatment outcomes, but no experimental data exist on whether this is efficacious. This double-blind randomised controlled trial was designed to evaluate whether adding nicotine patches to varenicline improves withdrawal relief and short-term abstinence rates.



117 participants seeking help to stop smoking were randomly allocated to varenicline plus placebo patch or varenicline plus nicotine patch (15 mg/16 hour). Varenicline use commenced one week prior to the target quit date (TQD), patch use started on the TQD. Ratings of urges to smoke and cigarette withdrawal symptoms were collected weekly over 4 weeks post-TQD. Medication use and smoking status were established at 1, 4 and 12 weeks. Participants lost to follow-up were included as continuing smokers.



92% of participants used both medications during the first week after the TQD. The combination treatment generated no increase in nausea or other adverse effects. It had no overall effect on urges to smoke or on other withdrawal symptoms. The combination treatment did not improve biochemically validated abstinence rates at 1 week and 4 weeks post-TQD (69% vs 59%, p=0.28 and 60% vs 59%, p=0.91, in the nicotine patch and placebo patch arm, respectively), or self reported abstinence rates at 12 weeks (36% vs. 29%, p=0.39, NS).



The efficacy of varenicline was not enhanced by the addition of nicotine patches, although further trials would be useful to exclude the possibility of type II error.
Autonomous visual model building based on image crawling through internet search engines

In this paper, we propose an autonomous learning scheme to automatically build visual semantic concept models from the output data of Internet search engines without any manual labeling work. First of all, images are gathered by crawling through the Internet using a search engine such as Google. Then, we model the search results as "Quasi-Positive Bags" in the Multiple-Instance Learning (MIL) framework. We call this generalized MIL (GMIL). We propose an algorithm called "Bag K-Means" to find the maximum Diverse Density (DD) without the existence of negative bags. A cost function is found as K-Means with special "Bag Distance". We also propose a solution called "Uncertain Labeling Density" (ULD) which describes the target density distribution of instances in the case of quasi-positive bags. A "Bag Fuzzy K-Means" is presented to get the maximum of ULD. By this generalized MIL with ULD, the model for a particular concept is learned from the crawled images of the Internet search engines. Experiments show that our algorithm can get correct models for the concepts we are interested in. Compared to the original Google Image Search, our algorithm shows improved accuracy.
Phase I study of docetaxel (TXT) and 5-fluorouracil (5-FU) with concurrent radiotherapy in patients with advanced esophageal cancer.

This phase I study was designed to determine the maximum-tolerated dose (MTD) of docetaxel (TXT) and toxicities of combining weekly administration of TXT and continuous infusion of 5-fluorouracil (5-FU) with concomitant radiotherapy for advanced esophageal cancer.



Patients received TXT by i.v. infusion over 1 h on days 1, 8, 22 and 29. They were also given 5-FU 250 mg/m2/day by continuous infusion for 24 h on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40 and 43-45. Fractionated radiotherapy was performed on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40 and 43-45, and a total dose of 60 to 66 Gy was delivered. The starting dose level (Level 1) of TXT was set at 7.5 mg/m2. Dose escalation was conducted in increments of 25 mg/m2, until the dose reached Level 4 (15 mg/m2). At least three patients were enrolled at each level.



Seven patients (median age, 64 years) were enrolled. Six patients had stage III (T4NIMO) and one had stage IVb (T4N1M1b) esophageal cancer; six had squamous cell carcinoma and one had carcinosarcoma. No patient had received prior chemotherapy or radiotherapy, and two patients had undergone esophageal bypass surgery using a whole stomach tube without resection of primary or metastatic lesions. In the 7patients, the regimen was well-tolerated, with esophagitis as the most common toxicity (grade 3: n=1; grade 4: n=3). In general, hematological toxicity was mild. Dose-limiting toxicity (DLT) was observed at Level 2 (TXT 10 mg/m2) when three patients developed grade 4 esophagitis and this dose was deemed the MTD for this regimen. In the 7 assessable patients, the overall clinical response rate was 85.7%.



The MTD of TXT in this regimen was 10 mg/m2 and the recommended dose of TXT was 7.5 mg/m2. Although esophagitis was the dose-limiting and the most frequent toxicity, the regimen was safe and well-tolerated, and demonstrated the possibility of good efficacy in patients with advanced esophageal cancer.
No glycemic benefit from guar administration in NIDDM.

A randomized crossover study of 5-g guar minitablets against placebo, given three times per day with main meals for 8 wk, was done in 29 non-insulin-dependent diabetes mellitus (NIDDM) patients who had near-normal fasting plasma glucose concentrations on treatment with diet alone, additional sulfonylurea, or ultralente insulin. Guar did not reduce the excessive postprandial glycemic excursion, glycosylated hemoglobin values, basal plasma glucose concentrations, basal or incremental plasma C-peptide values, or body weight. There were few side effects with either guar or placebo therapy. Mean low-density lipoprotein cholesterol levels were significantly reduced (P less than .001) by guar administration (116 +/- 23 vs. 104 +/- 19 mg/dl). Guar additives did not improve the excessive postprandial glycemia found in NIDDM patients in whom near-normal fasting plasma glucose levels had been obtained.
Odanacatib, a selective cathepsin K inhibitor to treat osteoporosis: safety, tolerability, pharmacokinetics and pharmacodynamics--results from single oral dose studies in healthy volunteers.

To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of odanacatib (ODN), a cathepsin K inhibitor, in humans.



Two double-blind, randomized, placebo-controlled, single oral dose studies were performed with ODN (2-600 mg) in 44 healthy volunteers (36 men and eight postmenopausal women).



Adverse experiences (AEs) with single doses of ODN were transient and mild to moderate, with the exception of one severe AE of gastroenteritis. Headache was the most frequent AE. After absorption of ODN (initial peak concentrations 4-6 h postdose), plasma concentrations exhibited a monophasic decline, with an apparent terminal half-life of ∼40-80 h. The area under the curve0-24 hours (AUC(0-24 h)), concentration at 24 hours (C(24 h)) and maximum concentration (C(max,overal)) increased in a less than dose-proportional manner from 2 to 600 mg. Administration of ODN with a high-fat meal led to ∼100% increases in AUC(0-24 h), C(max,day1), C(max,overall) and C(24 h) relative to the fasted state, while administration with a low-fat meal led to a ∼30% increase in those parameters. Reduction of biomarkers of bone resorption, the C- and N-telopeptides of cross-links of type I collagen, (CTx and NTx, respectively), was noted at 24 h for doses ≥5 mg and at 168 h postdose for ≥10 mg. In postmenopausal women administered 50 mg ODN, reductions in serum CTx of -66% and urine NTx/creatinine (uNTx/Cr) of -51% relative to placebo were observed at 24 h. At 168 h, reductions in serum CTx (-70%) and uNTx/Cr (-78%) were observed relative to baseline. Pharmacokinetic/pharmacodynamic modeling characterized the ODN concentration/uNTx/Cr relation, with a modeled EC50 value of 43.8 nM and ∼80% maximal reduction.



Odanacatib was well tolerated and has a pharmacokinetic and pharmacodynamic profile suitable for once weekly dosing.
Quality of Life After Isolated Limb Infusion for In-Transit Melanoma of the Extremity

Isolated limb infusion (ILI) has been associated with persistent edema, numbness, pain, and functional impairment of the treated limb. However, health-related quality of life (HRQOL) has not yet been assessed using a validated questionnaire.  questionnaires were collected from subjects enrolled a phase I ILI trial with temozolomide at baseline and 2, 6 weeks, and 3 months post-ILI. Of 28 enrolled patients, 19 patients received maximum tolerated dose of temozolomide and are included in the HRQOL analysis. Clinical and operative variables and treatment response data also were collected. HRQOL scores showed a trend of improvement from baseline through 3-months post-ILI as measured by FACT-M and the melanoma surgery scores. There were no differences in HRQOL when patients were stratified by disease burden, clinical toxicity level, and 3-month disease response. Additionally, fewer patients complained of pain, numbness, and swelling of the affected limb at 3 months post-ILI compared to baseline, and also these symptoms were improved at the immediate postoperative visit compared with baseline. Despite the known morbidity of ILI, we have demonstrated with a validated HRQOL questionnaire that HRQOL is not adversely impacted at therapeutic doses of temozolomide delivered intra-arterially from baseline through 3 months posttreatment. Patient centered-outcomes should be evaluated as a standard part of all future regional therapy trials using standardized melanoma-specific HRQOL questionnaires to more completely evaluate the utility of this type of treatment strategy.
Polymorphism in KIF6 gene and benefit from statins after acute coronary syndromes: results from the PROVE IT-TIMI 22 study.

We explored whether the benefit of intensive versus moderate statin therapy would be greater in carriers of KIF6 719Arg than in noncarriers.



The 719Arg variant of Trp719Arg (rs20455), a polymorphism in kinesin-like protein 6, is associated with greater risk of coronary events and greater benefit from pravastatin versus placebo.



We genotyped 1,778 acute coronary syndrome patients within the PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection  Thrombolysis in Myocardial Infarction 22) trial and investigated different intensities of statin therapy in carriers of 719Arg and in noncarriers using Cox proportional hazards models that adjusted for traditional risk factors.



Benefit from intensive, compared with moderate, statin therapy was significantly greater in the 59% of the cohort who were carriers (hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.45 to 0.77) than in those who were noncarriers (HR 0.94, 95% CI 0.70 to 1.27; p = 0.018 for interaction between 719Arg carrier status and treatment). Absolute risk reduction was 10.0% in carriers versus 0.8% in noncarriers. The benefit of intensive therapy in carriers was significant as early as day 30 of therapy. Carriers and noncarriers did not differ in on-treatment low-density lipoprotein cholesterol, triglyceride, or C-reactive protein (CRP) levels.



Carriers of 719Arg receive significantly greater benefit from intensive statin therapy than do noncarriers, a superior benefit that appears to be due to a mechanism distinct from lipid or CRP lowering. Functional studies of the KIF6 kinesin are warranted, given the consistent association of Trp719Arg with risk of coronary events and statin benefit.
A randomized multicenter study comparing a paclitaxel drug-eluting balloon with a paclitaxel-eluting stent in small coronary vessels: the BELLO (Balloon Elution and Late Loss Optimization) study.

The aim of this study was to evaluate the efficacy of drug-eluting balloons (DEB) compared with paclitaxel-eluting stents (PES) for the reduction of restenosis in small vessels.



DEB have been shown to be effective in the treatment of coronary in-stent restenosis, but data are limited regarding their efficacy in de novo disease.



BELLO (Balloon Elution and Late Loss Optimization) is a prospective, multicenter trial that randomized 182 patients with lesions located in small vessels (reference diameter <2.8 mm) to treatment with paclitaxel DEB and provisional bare-metal stenting (n = 90) or PES implantation (n = 92). The primary endpoint was noninferiority of angiographic in-stent (in-balloon) late loss with a delta of 0.25 mm. Secondary endpoints were angiographic restenosis, target lesion revascularization, and major adverse cardiac events (MACE; death, myocardial infarction, target vessel revascularization) at 6 months.



Baseline characteristics were well matched, except for a smaller vessel size in the DEB group (2.15 ± 0.27 mm vs. 2.25 ± 0.24 mm; p = 0.003). The majority (89%) of lesions involved vessels with a diameter <2.5 mm. Bailout stenting was required in 20% of lesions in the DEB group. The primary endpoint of in-stent (in-balloon) late loss was significantly less with DEB compared with PES (0.08 ± 0.38 mm vs. 0.29 ± 0.44 mm; difference -0.21; 95% CI: -0.34 to -0.09; p(noninferiority) < 0.001; p(superiority) = 0.001). At 6 months, DEB and PES were associated with similar rates of angiographic restenosis (10% vs. 14.6%; p = 0.35), [corrected] target lesion revascularization (4.4% vs. 7.6%; p = 0.37), and MACE (10% vs. 16.3%; p = 0.21). 
Treatment of small-vessel disease with a paclitaxel DEB was associated with less angiographic late loss and similar rates of restenosis and revascularization as a PES.
Alleviation of cancerous pain by external compress with Xiaozheng Zhitong Paste.

To observe the clinical effectiveness of a topical application of Xiaozheng Zhitong: Paste (, XZP) in alleviating the cancerous pain of patients with middle/late stage cancer



By: adopting a random number table, 124 patients enrolled were randomized into the treatment group (64 patients) and the control group (60 patients). In addition to the basic therapy [including the three-ladder (3L) analgesia] used in both groups, topical application of XZP was given to patients in the treatment group for pain alleviation. The analgesic efficacy was recorded in terms of pain intensity, analgesia initiating time and sustaining time, and the optimal analgesic effect revealing time. Meanwhile, the quality of life (QOL) and adverse reactions that occurred in patients were recorded as well.



The total effective rate in the treatment group was: 84.38% (54/64), and in the control group it was 88.33% (53/60), showing no significant difference between them (P>0.05), but the analgesia initiating time and the optimal analgesia effect revealing time in the treatment group were significantly shorter (both P<0.01). Moreover, XZP was better in improving patients' QOL, showing more significant improvements in the treatment group than those in the control group in aspects of mental condition, walking capacity, working capacity, social acceptability, sleep and joy of living (P<0.05 or P<0.01). Lower incidence of adverse reactions, such as nausea, vomiting, mouth dryness, dizziness, etc., especially constipation, was noted in the treatment group (P<0.05 or P<0.01).



Applying an external compress: of XZP showed a synergistic action with 3L analgesia for shortening the initiating time and the optimal effect revealing time, and could evidently enhance patients' QOL with fewer adverse reactions.
Performance tests in people with chronic low back pain: responsiveness and minimal clinically important change.

Cohort study.



To assess the responsiveness and minimal clinically important change (MCIC) of 6 commonly-used performance tests (5-minute walking, 50-ft walking, sit-to-stand, 1 minute stair climbing, loaded forward reach, Progressive Isoinertial Lifting Evaluation).



Performance tests are used to evaluate physical function in people with low back pain. Little is known about their clinimetric properties.



Performance tests were administered in people with chronic nonspecific low back pain (n = 198) before and after 10 weeks of treatment. At 10 weeks, the global perceived effect scale was used to determine if participants judged themselves as worsened, unchanged, or improved. The mean change scores for each performance test were calculated. A performance test was considered responsive if the area under the receiver operating characteristic curve (AUC) was equal to or greater than 0.70. We used 2 methods to evaluate MCIC: the optimal cut-off point based on the receiver operating characteristic curve, which takes into account both sensitivity and specificity, and the minimal detectable change for improvement, which considers test specificity only.



In general, the mean change scores were the smallest in participants who judged themselves worsened and largest in those reporting to be improved. Sit-to-stand (AUC = 0.75) and stair climbing (AUC = 0.72) were the only performance tests that showed adequate responsiveness. For sit-to-stand, the MCIC ranged from 4.1 to 9.8 seconds (19%-45% of the mean baseline score). For stair climbing, the MCIC ranged from 14.5 to 23.9 steps (19%-31% of the mean baseline score).



Only 2 of the 6 performance tests were responsive. Both had acceptable MCIC values. Developing individualized performance tests might partly overcome the general lack of responsiveness of performance tests. Future research should focus on the clinimetric testing of performance tests in subgroups.
Ventilatory and haemodynamic effects of terbutaline infusion during beta1-selective blockade with metoprolol and acebutolol in asthmatic patients

A double-blind, placebo-controlled study of the haemodynamic and ventilatory effects of two beta1-selective adrenoceptor blockers and their interaction with the beta2-adrenoceptor agonist terbutaline was carried out in eight asthmatic patients. One hour after intake of placebo, metoprolol 100 mg or acebutolol 400 mg, increasing doses of terbutaline were infused. Before and one hour after ingestion of the medication and after each infusion of terbutaline, ventilatory and haemodynamic indices were measured. The two beta-blocking agents caused equal changes in basal ventilatory and haemodynamic indices. Terbutaline infusion caused a dose-dependent increase in forced expiratory volume in one second (FEV1) and peak expiratory flow rate (PEFR), both during placebo and beta-blockade. Metoprolol did not affect the terbutaline-induced bronchodilatation. During acebutolol medication, however, the increase in FEV1 and PEFR induced by terbutaline was partly inhibited. Terbutaline infusion during placebo caused a dose-dependent increase in heart rate (HR) and systolic blood pressure (BP), and a decrease in diastolic BP. During acebutolol medication, these haemodynamic effects of terbutaline were completely blocked, but during metoprolol medication terbutaline still caused small changes in the same direction as during placebo, presumably because the vasodilator action of terbutaline was not inhibited. A negative correlation was found between the plasma levels of acebutolol and its metabolite N-acetyl acebutolol at the end of the study and changes in FEV1 and PEFR induced by terbutaline during acebutolol therapy as compared with placebo. The ventilatory and haemodynamic findings suggest a lower degree of beta1-selectivity after oral administration of acebutolol as compared to metoprolol.