nils-herrmann/clean_scirepeval huggingface dataset:
Serum MicroRNA-155 as a Potential Biomarker to Track Disease in Breast Cancer

One major impediment to improving the management of breast cancer is the current lack of tumor marker with sufficient sensitivity and specificity. A growing body of evidence implicates the diagnostic potential of circulating miRNAs in cancer detection. MiR-155 plays an important role in the pathogenesis of breast cancer. However, the level of circulating miR-155 and its clinical relevance are not well established. The objective of the current study was to learn more about serum miR-155 in patients with breast cancer.



Using quantitative reverse transcription polymerase chain reaction (RT-qPCR), we demonstrated that serum miR-155 had significant increased levels in breast cancer patients (n = 103) compared with healthy subjects (n = 55) (p<0.001), which had a mean fold change of 2.94. Receiver operating characteristic (ROC) analysis revealed that miR-155 had considerable diagnostic accuracy, yielding an ROC-AUC (the areas under the ROC curve) of 0.801 (sensitivity 65.0%, specificity 81.8%). In addition, sera from a subset of breast cancer patients (n = 29) were collected after surgery and after four cycles of chemotherapy to evaluate the effects of clinical treatment on serum levels of candidate miRNAs. Surprisingly, a decreased level of serum miR-155 was found; whereas the concentrations of carbohydrate antigen 15-3 (CA15-3), carcinoembryonic antigen (CEA) and tissue polypeptide specific antigen (TPS) did not show this trend. Our results revealed that 79% patients showed response or stable disease after therapy had declined levels of serum miR-155.



Our results suggest that serum miR-155 is a potential biomarker to discriminate breast cancer patients from healthy subjects. For the first time, we demonstrated a declined trend of miR-155 after surgery and chemotherapy, which raises the possibility to use it as an indicator for treatment response.
CE/BZA effects on bone and quality of life in European postmenopausal women: a pooled analysis.

To evaluate the efficacy of conjugated estrogens/bazedoxifene (CE/BZA) on bone mineral density (BMD), bone turnover markers (BTM), and menopause-specific quality of life (MENQOL) in European women.



Data through 12 months were pooled from two double-blind, randomized, controlled trials in non-hysterectomized postmenopausal women who received CE/BZA or placebo. Women from European study sites with evaluable BMD (n = 60), BTM (n = 56), and MENQOL questionnaire (n = 236) data were included and compared with 1523 women from US study sites (n = 730 with evaluable data for bone outcomes).



At month 12, CE 0.45 mg/BZA 20 mg and CE 0.625 mg/BZA 20 mg, respectively, significantly improved BMD (adjusted difference vs. placebo) in lumbar spine (2.5%, 2.9%; both p ≤ 0.011) and total hip (1.7%, 2.2%, both p ≤ 0.002), significantly improved serum BTMs (osteocalcin: -31.1%, -33.1%; C-telopeptide: -48.5%, -36.8%) vs. placebo (osteocalcin: 6.7%, C-telopeptide: 4.2%; all p < 0.001), and significantly improved MENQOL vasomotor function scores (-2.1, -2.2) vs. placebo (-0.7; both p < 0.001). No significant treatment × subpopulation interactions were observed for any of the outcomes.



Twelve-month CE/BZA treatment prevented bone loss and improved vasomotor function in European postmenopausal women. Findings were similar to those in the subpopulation of women enrolled at US study sites.
Central Sleep Apnoea Is Related to the Severity and Short-Term Prognosis of Acute Coronary Syndrome

To evaluate the relation of central sleep apnoea (CSA) to the severity and short-term prognosis of patients who experience acute coronary syndrome (ACS).



Observational study with cross-sectional and longitudinal analyses. Patients acutely admitted to participating hospitals because of ACS underwent respiratory polygraphy during the first 24 to 72 h. CSA was defined as an apnoea-hypopnoea index (AHI) >15 events•h-1 (>50% of central apnoeas). ACS severity (Killip class, ejection fraction, number of diseased vessels and peak plasma troponin) was evaluated at baseline, and short-term prognosis (length of hospitalization, complications and mortality) was evaluated at discharge.



A total of 68 CSA patients (AHI 31±18 events•h-1, 64±12 years, 87% males) and 92 controls (AHI 7±5 events•h-1, 62±12 years, 84% males) were included in the analyses. After adjusting for age, body mass index, hypertension and smoking status, patients diagnosed with CSA spent more days in the coronary unit compared with controls (3.7±2.9 vs. 1.5±1.7; p<0.001) and had a worse Killip class (Killip I: 16% vs. 96%; p<0.001). No differences were observed in ejection fraction estimates.



CSA patients exhibited increased ACS severity as indicated by their Killip classification. These patients had a worse prognosis, with longer lengths of stay in the coronary care units. Our results highlight the relevance of CSA in patients suffering ACS episodes and suggest that diagnosing CSA may be a useful strategy to improve the management of certain ACS patients.
A first-in-human dose-escalation study of ME-143, a second generation NADH oxidase inhibitor, in patients with advanced solid tumors

ME-143, a second-generation tumor-specific NADH oxidase inhibitor, is broadly active against human cancers in vitro and in vivo. This first-in-human dose-escalation study evaluated the dose-limiting toxicities (DLTs), pharmacokinetics, safety, tolerability, and preliminary anti-tumor activity of ME-143 in patients with advanced solid tumors.  Patients with advanced solid tumors were treated in a 3 + 3 escalation design. ME-143 was administered via intravenous infusion on days 1, 8, and 15 of the first 28-day cycle, and weekly thereafter; the final cohort received twice-weekly treatment. Samples for pharmacokinetic analysis were collected during cycle 1. Treatment continued until disease progression or unacceptable toxicity.  Eighteen patients were treated: 2.5 mg/kg (n = 3); 5 mg/kg (n = 3); 10 mg/kg (n = 3); 20 mg/kg (n = 6); 20 mg/kg twice-weekly (n = 3). There were no DLTs observed. Nearly all treatment-related toxicities were grade 1/2, specifically (all grades) nausea (22 %) and fatigue (17 %). Two patients experienced infusion reactions at the 20 mg/kg dose level, one of which was grade 4. Stable disease was documented in three patients with colorectal cancer, cholangiocarcinoma, and anal cancer. Pharmacokinetic exposures were linear and dose-dependent, with a half-life of approximately 5 h. Conclusions ME-143 was well-tolerated when administered intravenously at the maximally administered/recommended phase 2 dose of 20 mg/kg once weekly to patients with advanced solid tumors. Though limited clinical activity was observed with monotherapy, inhibitors of tumor-specific NADH oxidase such as ME-143 may derive their greatest benefit in combination with cytotoxic chemotherapy.
High doses of vascular endothelial growth factor 165 safely, but transiently, improve myocardial perfusion in no-option ischemic disease.

Gene therapy can induce angiogenesis in ischemic tissues. The aim of this study was to assess safety, feasibility, and results, both clinical and on myocardial perfusion, of gene therapy in refractory angina. This was a phase I/II, prospective, temporal-controlled series, clinical trial. Thirteen patients were maintained for minimum 6 months under optimized clinical management, and then received intramyocardial injections of 2000 μg plasmid vascular endothelial growth factor 165 and were followed by single-photon emission computed tomography (SPECT), treadmill tests, Minnesota quality of life questionnaire (QOL), and New York Heart Association (NYHA) functional plus Canadian Cardiovascular Society (CCS) angina classifications. There were no deaths, early or late. During the optimized clinical treatment, we observed worsening of rest ischemia scores on SPECT (p<0.05). After treatment, there was a transitory increase in myocardial perfusion at the third-month SPECT under stress (pre-operative [pre-op] 18.38 ± 7.51 vs. 3 months 15.31 ± 7.30; p<0.01) and at the sixth month under rest (pre-op 13.23 ± 7.98 vs. 6 months: 16.92 ± 7.27; p<0.01). One year after, there were improvements in treadmill test steps (pre-op 2.46 ± 2.07 vs.12 months 4.15 ± 2.23; p<0.01) and oxygen consumption (pre-op 7.66 ± 4.47 vs.12 months 10.89 ± 4.65; p<0.05), QOL (pre-op 48.23 ± 18.35 vs.12 months 28.31 ± 18.14; p<0.01) scores, and CCS (pre-op 3 [3-3.5] vs.12 months 2 [1-2.5]; p<0.01) and NYHA (pre-op 3 [3-3] vs. 2 [2-2] vs. 12 months 2 [1-2]; p<0.01) classes. Gene therapy demonstrated to be feasible and safe in this advanced ischemic cardiomyopathy patient sample. There were improvements in clinical evaluation parameters, and a transitory increase in myocardial perfusion detectable by SPECT scintigraphy.
The radiation exposure from portal images during the course of breast radiotherapy.

To evaluate the radiation dose to the contralateral breast (CB) from portal images taken during the course of conventional whole breast irradiation (WBI) and partial breast irradiation (PBI).



The dose to CB from portal images was measured in a female anthropomorphic phantom with 12 thermoluminescent dosimeters placed in the contralateral (right) breast near the midline of the phantom. The average CB dose from portal imaging per monitor unit (MU) was calculated. Twenty WBI patients and 9 PBI patients were randomly selected to obtain the average total MU (ATMU), minimum and maximum MU used to obtain portal images during their treatment. The estimated radiation dose from portal imaging to CB was calculated as average total MU multiplied by average CB dose from portal imaging per MU.



In WBI, the mean dose and range from 20 patients to 2 points (ie, point 1 and 9 in ) nearest to the midline of the phantom were 22.9 (15.1-43.4) cGy, and 8.4 (5.5-15.9) cGy, respectively. The doses to other points ranged from 0.9 cGy to 5.7 cGy. The PBI portal imaging techniques gave a significantly higher dose to most points in CB than the WBI. The doses to all the points ranged from 4.1 cGy to 27.4 cGy. The orthogonal portals contributed over 99% of the dose to CB for all the points.
Phase II study of monthly pasireotide LAR (SOM230C) for recurrent or progressive meningioma.

A subset of meningiomas recur after surgery and radiation therapy, but no medical therapy for recurrent meningioma has proven effective.



Pasireotide LAR is a long-acting somatostatin analog that may inhibit meningioma growth. This was a phase II trial in patients with histologically confirmed recurrent or progressive meningioma designed to evaluate whether pasireotide LAR prolongs progression-free survival at 6 months (PFS6). Patients were stratified by histology (atypical [World Health Organization grade 2] and malignant [grade 3] meningiomas in cohort A and benign [grade 3] in cohort B).



Eighteen patients were accrued in cohort A and 16 in cohort B. Cohort A had median age 59 years, median Karnofsky performance status 80, 17 (94%) had previous radiation therapy, and 11 (61%) showed high octreotide uptake. Cohort B had median age 52 years, median Karnofsky performance status 90, 11 (69%) had previous radiation therapy, and 12 (75%) showed high octreotide uptake. There were no radiographic responses to pasireotide LAR therapy in either cohort. Twelve patients (67%) in cohort A and 13 (81%) in cohort B achieved stable disease. In cohort A, PFS6 was 17% and median PFS 15 weeks (95% confidence interval: 8-20). In cohort B, PFS6 was 50% and median PFS 26 weeks (12-43). Treatment was well tolerated. Octreotide uptake and insulin-like growth factor-1 levels did not predict outcome. Expression of somatostatin receptor 3 predicted favorable PFS and overall survival.



Pasireotide LAR has limited activity in recurrent meningiomas. The finding that somatostatin receptor 3 is associated with favorable outcomes warrants further investigation.



This study provides Class IV evidence that in patients with recurrent or progressive meningioma, pasireotide LAR does not significantly increase the proportion of patients with PFS at 6 months.
Folic acid and vitamin B12 are more effective than vitamin B6 in lowering fasting plasma homocysteine concentration in patients with coronary artery disease

To investigate whether vitamin B6 supplementation had a beneficial effect on lowering fasting plasma homocysteine concentrations in coronary artery disease (CAD) patients. A single-blind intervention study. The study was performed at the Taichung Veterans General Hospital, the central part of Taiwan. A total of 50 subjects were identified by cardiac catheterization to have at least 70% stenosis of one major coronary artery. In all, 42 patients successfully completed this study. Patients were randomly assigned to one of five groups and treated with a daily dose of placebo (n=8), 5 mg vitamin B6 (n=8), 10 mg vitamin B6 (n=8), 50 mg vitamin B6 (n=9), or 5 mg folic acid combined with 0.25 mg vitamin B12 (n=9) for 12 weeks. Nutrient intakes were recorded by using 24-h diet recalls when patients returned to the cardiology clinic before the intervention (week 0) and at week 12. Vitamin B6 status was assessed by direct measures (plasma pyridoxal 5′-phosphate) and indirect measures (erythrocyte alanine and aspartate aminotransaminase activity coefficient). Fasting plasma homocysteine, serum folic acid, and vitamin B12 were measured. Fasting plasma homocysteine concentration did not respond to high or low doses of vitamin B6 when compared with a placebo treatment after 12 weeks of supplementation. The mean fasting plasma homocysteine concentration, however, decreased significantly after 12 weeks of folic acid combined with vitamin B12 supplementation (P=0.047). Further, within group, mean fasting plasma homocysteine concentration was nonsignificantly increased by 25.5, 16.2, and 18.3% in placebo, 10 mg/day and 50 mg/day vitamin B6 supplemented groups, respectively; whereas folic acid combined with vitamin B12 supplementation significantly reduced fasting plasma homocysteine concentration by 32% (P<0.001).Conclusions: Our results indicate that vitamin B6 supplementation alone is less effective than folic acid combined with vitamin B12 in lowering plasma homocysteine concentrations in CAD patients. This study was supported by the National Science Council, Taiwan, Republic of China (NSC-91-2320-B-040-023).
Validation of a Quantitative Single-Subject Based Evaluation for Rehabilitation-Induced Improvement Assessment

The foreseen outcome of a rehabilitation treatment is a stable improvement on the functional outcomes, which can be longitudinally assessed through multiple measures to help clinicians in functional evaluation. In this study, we propose an automatic comprehensive method of combining multiple measures in order to assess a functional improvement. As test-bed, a functional electrical stimulation based treatment for foot drop correction performed with chronic post-stroke participants is presented. Patients were assessed on five relevant outcome measures before, after intervention, and at a follow-up time-point. A novel algorithm based on variables minimum detectable change is proposed and implemented in a custom-made software, combining the outcome measures to obtain a unique parameter: capacity score. The difference between capacity scores at different timing is thresholded to obtain improvement evaluation. Ten clinicians evaluated patients on the Improvement Clinical Global Impression scale. Eleven patients underwent the treatment, and five resulted to achieve a stable functional improvement, as assessed by the proposed algorithm. A statistically significant agreement between intra-clinicians and algorithm-clinicians evaluations was demonstrated. The proposed method evaluates functional improvement on a single-subject yes/no base by merging different measures (e.g., kinematic, muscular) and it is validated against clinical evaluation.
Simvastatin given for 3 days can inhibit thrombin generation and activation of factor V and enhance factor Va inactivation in hypercholesterolemic patients.

Thrombin Generation and Activation of Factor V and Enhance Factor Va Inactivation in Hypercholesterolemic Patients  The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, have been reported to exert multiple cholesterol-independent actions, including inhibition of blood coagulation, most likely attributable to downregulation of tissue factor (TF) expression.1 Previously, we have demonstrated that simvastatin inhibits blood clotting after a 3-month simvastatin  It is unknown how rapidly statin administration can influence thrombin formation, factor (F)V activation, and the proteolytic degradation of FVa. The aim of the current study was to assess early effects of statins on coagulant reactions. Fourteen men (mean age, 54.6 years) with LDL cholesterol levels 3.4 mmol/L (130 mg/dL), who were treated with lowdose aspirin (75 mg/d), participated in the study after giving informed written consent. At baseline and after 3 days of simvastatin administration (40 mg/d), coagulant reactions were assessed in blood collected every 30 seconds at the site of microvascular injury, as previously described.2,3 Using quantitative Western blotting, we evaluated the time-courses of FVa generation and FVa inactivation, along with thrombin formation. We also determined lipid profiles, C-reactive protein (CRP) levels, fibrinogen, and thrombin-antithrombin complexes (TAT) in peripheral venous blood (Dade Behring) with data expressed as mean SEM. Paired t test and Wilcoxon signed ranks test were used when appropriate to compare the differences before and after simvastatin treatment. Spearman rank correlation coefficients were calculated to test the association between two variables. A 3-day simvastatin administration significantly retarded prothrombin activation (P 0.002; Figure, A) and FVa heavy (P 0.027; Figure, B) and light chains (P 0.033; data not shown) at the site of hemostatic plug formation. Plasma TAT levels showed a tendency toward lower posttreatment values (P 0.1), and fibrinogen was unchanged. After simvastatin use, thrombin generation at the site of injury slowed from 0.258 0.017 to 0.176 0.014 nmol/L/s (P 0.006), whereas the maximum rate of FVa heavy chain forma-
Initial energy for external electrical cardioversion of atrial fibrillation.

To investigate the initial energy level required for electrical cardioversion of atrial fibrillation (AF).



We studied patients undergoing electrical cardioversion in the 1st Multicenter Trial of SOCESP. Patients were divided into 2 groups according to the initial energy level of electrical cardioversion: 100J and >/=150J. We compared the efficacy of the initial and final shock of the procedure, the number of shocks administered, and the cumulative energy levels.



Eight-six patients underwent electrical cardioversion. In 53 patients (62%), cardioversion was started with 100J, and in 33 patients (38%), cardioversion was started with >/=150J. Groups did not differ regarding clinical features and therapeutical interventions. A tendency existed towards greater efficacy of the initial shock in patients who received >/=150J (61% vs. 42% in the 100J group, p=0.08). The number of shocks was smaller in the >/=150J group (1.5+/-0.7 vs. 2.1+/-1.3, p=0.04). No difference existed regarding the final efficacy of electrical cardioversion and total cumulative energy levels in both groups. In the subgroup of patients with recent-onset AF (</=48h), the cumulative energy level was lower in the 100J group (240+/-227J vs. 324+/-225J, p=0.03).



Patients who were given initial energy of >/=150J received fewer counter shocks with a tendency toward greater success than those patients who were given 100J; however, in patients with recent-onset AF, the average cumulative energy level was lower in the 100J group. These data suggest that electrical cardioversion should be initiated with energy levels >/=150J in patients with chronic AF.
Evaluation of a community intervention program in Japan using Framingham risk score and estimated 10-year coronary heart disease risk as outcome variables: a non-randomized controlled trial

Community-based programs are being widely adopted in the struggle to prevent cardiovascular diseases. No study has been conducted in Japan to evaluate the effects of a community-based health promotion program by using the Framingham risk score and 10-year CHD risk as outcome variables. The aim of the present study was to assess the effects of a program involving 6-month intervention and 18-month follow-up using such outcomes.



Participants (n = 1,983, 39.5% women, mean age 63.4 years) were selected for the study in 2008. Of these 1,983, 347 (42.4% women) subjects received the 6-month intervention. The intervention included individual counseling and group sessions, among others. After 18 months, 1,278 participants (intervention group: 238, control group: 1,040) were followed up. Changes in the Framingham risk score and 10-year coronary heart disease (CHD) risk were evaluated. ANCOVA and multiple logistic models adjusted for baseline value, age, sex and intervention times were used.



The results showed that the differences in the Framingham risk score and mean 10-year CHD risk were significant in the intervention group compared with the control group after 6-month follow-up (-0.46 and -1.12, respectively) and were also significant after 18-month follow-up (-0.39 and -0.85, respectively). The proportion of those with intermediate 10-year CHD risk (> = 10%) was significantly lower at 6 months (OR 0.30, 95% CI 0.12-0.74) and at 18 months (OR 0.41, 95% CI 0.19-0.92).



The six-month intervention program effectively decreased estimated 10-year CHD risk and the effects were still present at 18-month follow-up.
Medical dispatchers recognise substantial amount of acute stroke during emergency calls

Immediate recognition of stroke symptoms is crucial to ensure timely access to revascularisation therapy. Medical dispatchers ensure fast admission to stroke facilities by prioritising the appropriate medical response. Data on medical dispatchers' ability to recognise symptoms of acute stroke are therefore critical in organising emergency stroke care. We aimed to describe the sensitivity and positive predictive value of medical dispatchers' ability to recognise acute stroke during emergency calls, and to identify factors associated with recognition.



This was an observational study of 2653 consecutive unselected patients with a final diagnosis of stroke or transient ischemic attack (TIA). All admitted through the Emergency Medical Services Copenhagen, during a 2-year study period (2012-2014). Final diagnoses were matched with dispatch codes from the Emergency Medical Dispatch Centre. Sensitivity and positive predictive value were calculated. The effect of age, gender, and time-of-day was analysed using multivariable logistic regression.



The sensitivity was 66.2 % (95 % CI: 64.4 %-68.0 %), and the positive predictive value was 30.2 % (95 % CI: 29.1 %-31.4 %). The multivariable logistic regression analyses showed that emergency calls during daytime and a final diagnosis of TIA vs. intracerebral haemorrhage (ICH), was positively associated with recognition of stroke (OR 2.70, 95 % CI: 2.04-3.57).



This study reports a high rate of stroke recognition compared to other studies ranging from 31% to 74%. The high sensitivity is likely the result of a profound reorganisation of the Emergency Medical ServicesCopenhagen, including the introduction of EMDs with a medical profession, and a criteria-based dispatch tool. A recognition rate of 100 % is not obtainable without an inappropriate amount of false positive cases.



We report an overall high recognition of stroke by medical dispatchers. A final diagnosis of TIA, compared to ICH, was positively associated with recognition of acute stroke. Emergency medical dispatchers serve as the essential first step in ensuring fast-track stroke treatment, which would promote timely acute therapy.