nils-herrmann/clean_scirepeval huggingface dataset:
Colesevelam hydrochloride (cholestagel): a new, potent bile acid sequestrant associated with a low incidence of gastrointestinal side effects.

To compare colesevelam hydrochloride (Cholestagel), a nonabsorbed hydrogel with bile acid-sequestering properties, with placebo for its lipid-lowering efficacy, its effects on laboratory and clinical safety parameters, and the incidence of adverse events.



Following diet and placebo lead-in periods, placebo or colesevelam was administered at 4 dosages (1.5, 2.25, 3.0, or 3.75 g/d) for 6 weeks with morning and evening meals to men and women with hypercholesterolemia (low-density lipoprotein cholesterol level >4.14 mmol/L [>160 mg/dL]). Patients returned to the clinic every 2 weeks throughout the treatment period for lipid parameter measurements and adverse event assessments. Samples were collected for serum chemistry profiles, hematologic studies, coagulation studies, and vitamin level assessment at baseline and after 6 weeks of treatment.



Among the 149 patients randomized, 137 completed the study. Low-density lipoprotein cholesterol concentrations decreased in a dosage-dependent manner by 0.11 mmol/L (4.2 mg/dL) (1.8%) in the 1.5-g/d colesevelam treatment group and up to 1.01 mmol/L (39 mg/dL) (19.1%) in the 3.75-g/d colesevelam treatment group. Low-density lipoprotein cholesterol concentrations at the end of treatment were significantly reduced from baseline levels in the 3.0- and 3.75-g/d colesevelam treatment groups (P = .01 and P<.001, respectively). Total cholesterol levels demonstrated a similar response to colesevelam treatment, with an 8. 1% decrease from baseline in the 3.75-g/d treatment group (P<.001). High-density lipoprotein cholesterol levels rose significantly in the 3.0- and 3.75-g/d colesevelam treatment groups, by 11.2% (P=.006) and 8.1% (P=.02), respectively. Median triglyceride levels did not change from baseline, nor were there any significant differences between treatment groups. The incidence of adverse events was similar among all groups.



Colesevelam therapy is effective for lowering low-density lipoprotein cholesterol concentrations in persons with moderate hypercholesterolemia. It lacks the constipating effect of other bile acid sequestrants, demonstrating the potential for increased compliance.
Biological mediators of effect of diet and stress reduction on prostate cancer.

A 6-month pilot intervention trial was conducted to determine whether adoption of a plant-based diet, reinforced by stress reduction, could reduce the rate of prostate-specific antigen (PSA) increase, a marker of disease progression, in asymptomatic, hormonally untreated patients experiencing consistently increasing PSA levels after surgery or radiation.



A pre-post design was used to examine (1) the effect of intervention on potential mediators of disease progression, including body composition and weight-related biomarkers (sex steroid hormones and cytokines), and (2) whether changes in these variables were associated with change in rate of PSA increase. The baseline rate of PSA increase (from the time of posttreatment recurrence to the start of intervention) was ascertained from medical records. Body composition and biomarkers were assessed at baseline (prior to intervention), during the intervention (3 months), and at the end of the intervention (6 months). Changes in body composition and biomarkers were determined and compared with rates of PSA increase over the corresponding time intervals.



There was a significant reduction in waist-to-hip ratio (P=.03) and increase in circulating sex hormone binding globulin (P=.04). The rate of PSA increase decreased from the preintervention period (PSA slope=0.059) to the period from 0 to 3 months (PSA slope=0.002, P<.01) and increased slightly, although not significantly, from 0 to 3 months to the period from 3 to 6 months (0.029, P=.43).



Adoption of a plant-based diet and stress reduction may reduce central adiposity and improve the hormonal milieu in patients with recurrent PC. Changes in the rate of increase in PSA were in the same direction as changes in waist-to-hip ratio and opposite those of sex hormone binding globulin, raising the possibility that the effect of the intervention may have been mediated, in part, by these variables.
Lipopolysaccharide amplifies eosinophilic inflammation after segmental challenge with house dust mite in asthmatics.

House dust contains mite allergens as well as bacterial products such as lipopolysaccharide (LPS). Asthma exacerbations are associated with the level of exposure to allergens and LPS. LPS can potentiate allergen effects in steroid-naïve patients. Long-acting β2-agonists (LABA) were shown to inhibit LPS-induced bronchial inflammation in healthy volunteers. The aim of this study was to assess the effect of LPS on the allergen-induced eosinophilic inflammation [primary endpoints: eosinophil counts and eosinophil cationic protein (ECP)] induced by bronchial instillation of house dust mite (HDM) in patients with asthma on maintenance treatment with inhaled corticosteroids (ICS).



Thirty-two nonsmoking asthmatics with HDM allergy were treated with run-in medication (fluticasone propionate 100 μg bid) during 2 weeks before the study day. All patients underwent bronchial challenge with HDM, and half of them were randomized to receive additional LPS. Both groups were randomized to receive pretreatment with a single inhalation of 100 μg salmeterol 30 min before bronchial segmental challenge. Six hours later, bronchoalveolar lavage (BAL) was collected for leukocyte cell count, differentials, and cellular activation markers.



Challenge with HDM/LPS induced a significant increase in eosinophil cationic protein (P = 0.036) and a trend toward an increase in BALF eosinophils as compared to HDM challenge.



Lipopolysaccharide promotes eosinophilic airway inflammation in patients with asthma despite being on maintenance treatment with ICS.
Free reactive oxygen species and nephrotoxicity of contrast agents.

The nephrotoxicity induced by contrast media remains a serious clinical problem, and the underlying mechanism has not been completely understood. Experimental and clinical investigations suggest that reactive oxygen species (ROS) are critical determinants of radiocontrast nephropathy (RCN), and that antioxidants can prevent this damage.



Cultured human proximal renal tubule cells (HK-2) were exposed to hydrogen peroxide (H2O2) at different concentrations. H2O2-induced tubular DNA damage was examined in the presence of the antioxidant MESNA (sodium-2-mercaptoethane sulphonate). The induction of DNA damage was measured with the alkaline comet assay (single cell gel electrophoresis). We also studied 12 patients with stable renal impairment (median baseline creatinine 296 micromol/l; range: 203-495 micromol/l) undergoing cardiac catheterization/intervention prospectively. Patients received 800 mg MESNA intravenously 30 min before exposure to the contrast agent in addition to 0.9% saline hydration.



In the cell cultures, oxidative stress on HK-2 cells induced increased DNA migration in the comet assay. Treatment of tubular cells with the antioxidant MESNA prior to the addition of H2O2 significantly reduced DNA migration in the comet assay. In the clinical study, treatment of the patients with MESNA prevented the adverse renal effect of contrast media (median serum creatinine 293; range: 187-433 micromol/l) 48 h after coronary angiography/intervention.



Both the in vivo and the in vitro studies suggest that the ROS-mediated renal injury could be inhibited by a potent antioxidant such as MESNA.
Electrophysiological Studies in Patients with Pulmonary Hypertension: A Retrospective Investigation

Few studies have investigated patients with pulmonary hypertension and arrhythmias. Data on electrophysiological studies in these patients are rare. In a retrospective dual-centre design, we analysed data from patients with indications for electrophysiological study. Fifty-five patients with pulmonary hypertension were included (Dana Point Classification: group 1: 14, group 2: 23, group 3: 4, group 4: 8, group 5: 2, and 4 patients with exercised-induced pulmonary hypertension). Clinical data, 6-minute walk distance, laboratory values, and echocardiography were collected/performed. Nonsustained ventricular tachycardia was the most frequent indication (n = 15) for an electrophysiological study, followed by atrial flutter (n = 14). In summary 36 ablations were performed and 25 of them were successful (atrial flutter 12 of 14 and atrioventricular nodal reentrant tachycardia 4 of 4). Fluoroscopy time was 16 ± 14.4 minutes. Electrophysiological studies in patients with pulmonary hypertension are feasible and safe. Ablation procedures are as effective in these patients as in non-PAH patients with atrial flutter and atrioventricular nodal reentrant tachycardia and should be performed likewise. The prognostic relevance of ventricular stimulations and inducible ventricular tachycardias in these patients is still unclear and requires further investigation.
Oral vitamin D 3 and calcium for secondary prevention of low-trauma fractures in elderly people ( Randomised Evaluation of Calcium Or vitamin D , RECORD ) : a randomised placebo-controlled trial

Low-trauma fractures in elderly people are a substantial and increasing burden of ill health, and those who have a low-trauma fracture are at high risk of another. Low serum concentrations of vitamin D metabolites are widespread in elderly people in the UK, especially in those with low-trauma fractures. Vitamin D and calcium, alone or in combination, are often recommended for prevention of osteoporotic fractures. Inadequate vitamin D status, exacerbated by low calcium intake, might raise the risk of these fractures by increasing bone resorption and loss from secondary hyperparathyroidism. Vitamin D might also protect against falls that lead to fracture. Evidence from randomised trials favours the combination of calcium and vitamin D. In this secondary-prevention study we aimed to test whether calcium and vitamin D, alone or in combination compared with placebo, would lead to one less person per 100 having a fracture every year over a median of 3 years.  Participants 15 024 people age 70 years or older who had had a lowtrauma, osteoporotic fracture in the previous 10 years were assessed between Feb 1, 1999, and March 31, 2002. The trial was based in 21 hospitals in the UK. Ethics approval was obtained from the Multicentre Research Ethics Committee for Scotland and from the local research ethics committee of each hospital, and participants gave written informed consent. Study nurses identified potential participants from hospital notes of patients seen in a fracture clinic or orthopaedic ward; patients were also recruited by telephone. Reasons for exclusion were: bed or chair bound before fracture; cognitive impairment indicated by an abbreviated mental test score of less than seven; cancer in the past 10 years that was likely to metastasise to bone; fracture associated with pre-existing local bone abnormality; those known to have hypercalcaemia; renal stone in the past 10 years; life expectancy of less than Published online April 28, 2005 DOI: 10.1016/S0140-6736(05) 63013-9
Agent-Human Interactions in the Continuous Double Auction

The Continuous Double Auction (CDA) is the dominant market institution for real-world trading of equities, commodities, derivatives, etc. We describe a series of laboratory experiments that, for the first time, allow human subjects to interact with software bidding agents in a CDA. Our bidding agents use strategies based on extensions of the Gjerstad-Dickhaut and Zero-Intelligence-Plus algorithms. We find that agents consistently obtain significantly larger gains from trade than their human counterparts. This was unexpected because both humans and agents have approached theoretically perfect efficiency in prior all-human or allagent CDA experiments. Another unexpected finding is persistent far-from-equilibrium trading, in sharp contrast to the robust convergence observed in previous all-human or all-agent experiments. We consider possible explanations for our empirical findings, and speculate on the implications for future agent-human interactions in electronic markets.
A study of the utility and equivalency of 2 methods of wound measurement: digitized tracing versus digital photography.

To examine agreement between digitized tracing and digital photography methods in measuring wound area and healing rate, and to compare and contrast the 2 methods on feasibility and utility in patient care and research settings.



Toronto Rehabilitation Institute, University Health Network, Toronto, Ontario, Canada.



A total of 20 subjects aged 18 years or older with a spinal cord injury and pressure ulcers that were Stage II or higher, and who had received in- or outpatient wound care at the hospital for at least 3 consecutive weeks.



Wound area was measured at weekly intervals. One assessor calculated wound area from a digitized tracing. A second assessor calculated wound area using a wound photograph. Both assessors used Image-J software. The 2 methods were compared for differences in weekly wound area and weekly healing rate.



Methods were different for wound area (P < .0001), whereas there was no difference between methods in weekly healing rate (P = .9429).



The 2 methods are in agreement on the important parameter of healing rate. Both methods are feasible in clinical settings. Wound photography may be more useful than digitized tracings because it simultaneously captures wound appearance.
TBCRC 008: early change in 18F-FDG uptake on PET predicts response to preoperative systemic therapy in human epidermal growth factor receptor 2-negative primary operable breast cancer.

Epigenetic modifiers, including the histone deacetylase inhibitor vorinostat, may sensitize tumors to chemotherapy and enhance outcomes. We conducted a multicenter randomized phase II neoadjuvant trial of carboplatin and nanoparticle albumin-bound paclitaxel (CP) with vorinostat or placebo in women with stage II/III, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, in which we also examined whether change in maximum standardized uptake values corrected for lean body mass (SUL(max)) on (18)F-FDG PET predicted pathologic complete response (pCR) in breast and axillary lymph nodes.



Participants were randomly assigned to 12 wk of preoperative carboplatin (area under the curve of 2, weekly) and nab-paclitaxel (100 mg/m(2) weekly) with vorinostat (400 mg orally daily, days 1-3 of every 7-d period) or placebo. All patients underwent (18)F-FDG PET and research biopsy at baseline and on cycle 1 day 15. The primary endpoint was the pCR rate. Secondary objectives included correlation of change in tumor SUL(max) on (18)F-FDG PET by cycle 1 day 15 with pCR and correlation of baseline and change in Ki-67 with pCR.



In an intent-to-treat analysis (n = 62), overall pCR was 27.4% (vorinostat, 25.8%; placebo, 29.0%). In a pooled analysis (n = 59), we observed a significant difference in median change in SUL(max) 15 d after initiating preoperative therapy between those achieving pCR versus not (percentage reduction, 63.0% vs. 32.9%; P = 0.003). Patients with 50% or greater reduction in SUL(max) were more likely to achieve pCR, which remained statistically significant in multivariable analysis including estrogen receptor status (odds ratio, 5.1; 95% confidence interval, 1.3-22.7; P = 0.023). Differences in baseline and change in Ki-67 were not significantly different between those achieving pCR versus not.



Preoperative CP with vorinostat or placebo is associated with similar pCR rates. Early change in SUL(max) on (18)F-FDG PET 15 d after the initiation of preoperative therapy has potential in predicting pCR in patients with HER2-negative breast cancer. Future studies will further test (18)F-FDG PET as a potential treatment-selection biomarker.
Prevalence of trait anxiety in a sample of depressed inpatients and its influence on response to antidepressants.

Depression and anxiety frequently occur together or in extension of each other. According to a previous study in depressed inpatients, a high trait anxiety level correlated with a positive response to the diazepam test (DT) and a low trait anxiety level with a negative response to the test. The aim of this study is to investigate whether positive reaction to the DT is related to a positive response to fluvoxamine and whether a negative reaction to the test is related to positive response to imipramine. The DT was performed in 130 patients diagnosed with a depressive disorder. Following the DT, the patients were randomly assigned to double-blind treatment with either imipramine or fluvoxamine. Doses of both antidepressants were adjusted to attain predefined blood levels, and the outcome was evaluated 4 weeks after attaining these blood levels. Twenty-two patients had a positive response to the DT, whereas 108 patients had a negative response. Although a positive DT is correlated with a high level of trait anxiety, no differences in depressive symptomatology and antidepressant response were found between patients with a positive and a negative DT.
Validating Automotive Control Software Using Instrumentation-Based Verification

This paper discusses the results of an application of a formally based verification technique, called Instrumentation-Based Verification (IBV), to a production automotive lighting controller. The goal of the study is to assess, from both a tools as well as a methodological perspective, the performance of IBV in an industrial setting. The insights obtained as a result of the project include a refinement of a previously developed architecture for requirements specifications; observations about changes to model-based design workflows; insights into the role of requirements during development; and the capability of automated verification to detect inconsistencies among requirements as well as between requirements and design models.
Fish consumption and markers of colorectal cancer risk : a multicenter randomized controlled trial 1 – 3

Diet is a major factor in the etiology of colorectal cancer, with high fish consumption possibly decreasing colorectal cancer risk, as was shown in several observational studies. To date, no intervention trials have examined the possible beneficial effects of fish intake on colorectal cancer risk.  The objective was to investigate the effects of a 6-mo intervention with oil-rich or lean fish on apoptosis and mitosis within the colonic crypt.  In a multicenter, randomized, controlled intervention trial, patients with colorectal polyps, inactive ulcerative colitis, or no macroscopic signs of disease were recruited (n = 242) and randomly allocated to receive dietary advice plus either 300 g oil-rich fish (salmon) per week (n = 82), 300 g lean fish (cod) per week (n = 78), or only dietary advice (DA) (n = 82). Apoptosis and mitosis were measured in colonic biopsy samples collected before and after intervention (n = 213).  The total number of apoptotic cells per crypt did not increase in the salmon or cod group: 20.10 (95% CI: 20.36, 0.16) and 20.06 (95% CI: 20.32, 0.20), respectively, compared with the DA group. The total number of mitotic cells per crypt decreased nonsignificantly in the salmon group (20.87; 95% CI: 22.41, 0.68) and in the cod group (21.04; 95% CI: 22.62, 0.53) compared with the DA group. Furthermore, the distribution of mitosis within the crypt did not significantly change in either group.  An increase in the consumption of either oil-rich or lean fish to 2 portions weekly over 6 mo does not markedly change apoptotic and mitotic rates in the colonic mucosa.
Interactive effects of childhood maltreatment and recent stressful life events on alcohol consumption in adulthood.

Childhood maltreatment is associated with early alcohol use initiation, alcohol-related problem behaviors, and alcohol use disorders in adulthood. Heavy drinking risk among individuals exposed to childhood maltreatment could be partly attributable to stress sensitization, whereby early adversity leads to psychobiological changes that heighten sensitivity to subsequent stressors and increase risk for stress-related drinking. We addressed this issue by examining whether the association between past-year stressful life events and past-year drinking density, a weighted quantity-frequency measure of alcohol consumption, was stronger among adults exposed to childhood maltreatment.



Drinking density, stressful life events, and child maltreatment were assessed using structured clinical interviews in a sample of 4,038 male and female participants ages 20-58 years from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Stress sensitization was examined using hierarchical multiple regression analyses to test whether stressful events moderated the association between maltreatment and drinking density. Analyses were stratified by sex and whether the impact was different for independent stressful events or dependent stressful events as related to a participant's actions.



Independent stressful events were associated with heavier drinking density among women exposed to maltreatment. In contrast, drinking density was roughly the same across independent stressful life events exposure among women not exposed to maltreatment. There was little evidence for Maltreatment × Independent Stressor interactions in men or Maltreatment × Dependent Stressor interactions in either gender.



Early maltreatment may have direct effects on vulnerability to stress-related drinking among women, particularly in association with stressors that are out of one's control.
Feasibility of and rectal dosimetry improvement with the use of SpaceOAR® hydrogel for dose-escalated prostate cancer radiotherapy.

The aim of this study was to investigate the feasibility of injecting a temporary spacer between the rectum and the prostate and to quantify the degree of rectal dosimetric improvement that might result.



Ten patients underwent CT and MRI before and after injection of 10 cc of hydrogel and at completion of radiotherapy. Hydrogel was injected under general anaesthetic using a transperineal approach. The primary endpoints were perioperative toxicity and rectal dosimetry (V80, V75, V70, V65, V40 and V30). Secondary endpoints were acute gastrointestinal toxicity during and 3 months following radiotherapy and the stability of the hydrogel. Treatment for all patients was planned incorporating volumetric modulated arc therapy with a D95 of 80 Gy in 40 fractions to the prostate and proximal seminal vesicles on both the pre- and post-hydrogel scans. Toxicity was scored with the Common Terminology Criteria, v. 3.0.



In the first 24 h, two patients described an increase in bowel movement frequency. The comparison plans had identical prescription doses. Rectal doses were significantly lower for all hydrogel patients for all dose endpoints (V80 = 7% vs. 0.1%, V75 = 10.3% vs. 1.1%, V70 = 13.2% vs. 2.7%, V65 = 15.8% vs. 4.6%, V40 = 35.2% vs. 23.3%, V30 = 52.6% vs. 38.5%; P < 0.001). Post-treatment MRI showed gel stability. Grade 1 bowel toxicity was reported in six patients during radiotherapy and two patients at 3 months' follow-up. No Grade 2 or Grade 3 acute bowel toxicity was reported.



SpaceOAR hydrogel was successfully injected in 10 patients with minimal side effects. Rectal dosimetry was significantly improved in all patients. This study has been extended to 30 patients with longer follow-up planned.