nils-herrmann/clean_scirepeval huggingface dataset:
Total Exposure Study Analysis consortium: a cross-sectional study of tobacco exposures

The Total Exposure Study was a stratified, multi-center, cross-sectional study designed to estimate levels of biomarkers of tobacco-specific and non-specific exposure and of potential harm in U.S. adult current cigarette smokers (≥one manufactured cigarette per day over the last year) and tobacco product non-users (no smoking or use of any nicotine containing products over the last 5 years). The study was designed and sponsored by a tobacco company and implemented by contract research organizations in 2002-2003. Multiple analyses of smoking behavior, demographics, and biomarkers were performed. Study data and banked biospecimens were transferred from the sponsor to the Virginia Tobacco and Health Research Repository in 2010, and then to SRI International in 2012, for independent analysis and dissemination.



We analyzed biomarker distributions overall, and by biospecimen availability, for comparison with existing studies, and to evaluate generalizability to the entire sample. We calculated genome-wide statistical power for a priori hypotheses. We performed clinical chemistries, nucleic acid extractions and genotyping, and report correlation and quality control metrics.



Vital signs, clinical chemistries, and laboratory measures of tobacco specific and non-specific toxicants are available from 3585 current cigarette smokers, and 1077 non-users. Peripheral blood mononuclear cells, red blood cells, plasma and 24-h urine biospecimens are available from 3073 participants (2355 smokers and 719 non-users). In multivariate analysis, participants with banked biospecimens were significantly more likely to self-identify as White, to be older, to have increased total nicotine equivalents per cigarette, decreased serum cotinine, and increased forced vital capacity, compared to participants without. Effect sizes were small (Cohen's d-values ≤ 0.11). Power for a priori hypotheses was 57 % in non-Hispanic Black (N = 340), and 96 % in non-Hispanic White (N = 1840), smokers. All DNA samples had genotype completion rates ≥97.5 %; 68 % of RNA samples yielded RIN scores ≥6.0.



Total Exposure Study clinical and laboratory assessments and biospecimens comprise a unique resource for cigarette smoke health effects research. The Total Exposure Study Analysis Consortium seeks to perform molecular studies in multiple domains and will share data and analytic results in public repositories and the peer-reviewed literature. Data and banked biospecimens are available for independent or collaborative research.
Acceptability and satisfaction with a telecarer approach to the management of type 2 diabetes.

To examine patients' views of the acceptability of and satisfaction with telephone care center support provided to improve blood glucose control in type 2 diabetes.



The Pro-Active Call-Center Treatment Support (PACCTS) Trial randomized patients from 47 general practices in a deprived urban area in northwest England to usual care or to proactive call center support in addition to usual care. Satisfaction with care was assessed in all 591 patients at baseline and the end of the study using the Diabetes Satisfaction and Treatment Questionnaire (DTSQ). Acceptability was assessed in 394 intervention patients after at least three proactive calls from the call center and at the end of the trial. A purposive sample of 25 patients took part in in-depth semistructured interviews.



The response rates to the questionnaires were 79% (DTSQ) and 65% (acceptability). Persons receiving the intervention continued to report high levels of satisfaction with their treatment (95% CI 32.3-33.2 at 1 year), and >90% strongly agreed or agreed that the telecarer approach was acceptable. Qualitative comments pointed to the importance of a personalized service; increased feelings of well-being, including confidence and self-control; help with problem-solving; and patients developing rapport and a strong bond with the telecarers.



A personalized PACCTS approach is acceptable to patients. A service giving priority to the interpersonal dimension leads to increased commitment from patients to improve long-term glycemic control.
Rationale and design of the participant, investigator, observer, and data-analyst-blinded randomized AGENDA trial on associations between gene-polymorphisms, endophenotypes for depression and antidepressive intervention: the effect of escitalopram versus placebo on the combined dexamethasone-cortico

Endophenotypes are heritable markers, which are more prevalent in patients and their healthy relatives than in the general population. Recent studies point at disturbed regulation of the hypothalamic-pituitary-adrenocortical axis as a possible endophenotype for depression. We hypothesize that potential endophenotypes for depression may be affected by selective serotonin re-uptake inhibitor antidepressants in healthy first-degree relatives of depressed patients. The primary outcome measure is the change in plasma cortisol in the dexamethasone-corticotrophin releasing hormone test from baseline to the end of intervention.



The AGENDA trial is designed as a participant, investigator, observer, and data-analyst-blinded randomized trial. Participants are 80 healthy first-degree relatives of patients with depression. Participants are randomized to escitalopram 10 mg per day versus placebo for four weeks. Randomization is stratified by gender and age. The primary outcome measure is the change in plasma cortisol in the dexamethasone-corticotrophin releasing hormone test at entry before intervention to after four weeks of intervention. With the inclusion of 80 participants, a 60% power is obtained to detect a clinically relevant difference in the primary outcome between the intervention and the placebo group. Secondary outcome measures are changes from baseline to four weeks in scores of: 1) cognition and 2) neuroticism. Tertiary outcomes measures are changes from baseline to four weeks in scores of: 1) depression and anxiety symptoms; 2) subjective evaluations of depressive symptoms, perceived stress, quality of life, aggression, sleep, and pain; and 3) salivary cortisol at eight different timepoints during an ordinary day. Assessments are undertaken by assessors blinded to the randomization group.
Adiponectin and its response to thiazolidinediones are associated with insulin-mediated glucose metabolism in type 2 diabetic patients and their first-degree relatives.

Patients with type 2 diabetes (T2D) and their first-degree relatives (FDRs) are characterized by hypoadiponectinaema and insulin resistance. In T2D patients, plasma adiponectin and insulin sensitivity (SI) increase in response to thiazolidinediones (TZDs). These findings suggest a role for adiponectin in the regulation of SI. We studied the relationship between plasma adiponectin and glucose and lipid metabolism and the effect of troglitazone (200 mg/day) for 12 weeks in 19 normoglycaemic, obese FDR and 20 obese T2D patients, using euglycaemic-hyperinsulinaemic clamps, glycolytic flux calculations and indirect calorimetry. Plasma adiponectin was similar in both groups, despite higher glucose disposal (Rd), glucose oxidation and glycolytic flux and lower lipid oxidation during insulin stimulation in FDR compared with T2D patients. Plasma adiponectin correlated with insulin-stimulated Rd, non-oxidative glucose disposal (NOGD), glucose storage and SI in both groups after adjustment for sex and body fat. The troglitazone-mediated upregulation of plasma adiponectin was associated with increased insulin-stimulated Rd, NOGD and glucose storage in both groups. No effect on endogenous glucose production was observed. In FDR, plasma adiponectin correlated with insulin-stimulated glycogen synthase activity and the troglitazone-induced increase in plasma adiponectin correlated with the improvement in insulin-stimulated Rd and SI after adjustment for sex and body fat. In conclusion, plasma adiponectin in weight-matched FDR and T2D patients is comparably low and correlates with insulin-mediated glucose uptake and storage. Moreover, these data provide evidence for an adiponectin-dependent insulin-sensitizing effect of TZDs at an early stage before development of T2D and that this effect is exerted mainly on insulin-mediated glucose metabolism.
Influence of radiotherapy on the dose of adjuvant chemotherapy in early breast cancer

399 patients with early breast cancer were randomly allocated to treatment by either modified radical mastectomy or lumpectomy and radiotherapy. 169 had histologically involved axillary nodes and were randomised to receive either adjuvant cytotoxic chemotherapy (76 patients) or no systemic adjuvant treatment (93 patients). Chemotherapy comprised a combination of oral cyclophosphamide and intravenous methotrexate and 5-fluorouracil (CMF) for 12 cycles over one year. Patients in the mastectomy group received a significantly higher percentage of the planned chemotherapy dose compared with those in the radiotherapy group (median 85% v. 71% p < 0.05). Patients treated with radiotherapy were more frequently nauseated and developed more severe alopecia, but these differences were not statistically significant. At median follow-up of 37 months the relapse-rate and pattern of relapse were similar in both groups of patients receiving CMF.
Complement activation in patients with congestive heart failure: effect of high-dose intravenous immunoglobulin treatment.

Increasing evidence implicates innate immunity in the pathogenesis of congestive heart failure (CHF). In the present study, we examined the possible role of complement, an important part of innate immunity, in CHF.



Complement activation was analyzed in systemic and coronary circulation in 39 patients with CHF and 20 healthy control subjects. In a double-blind, placebo-controlled study, we have recently reported that high-dose intravenous immunoglobulin (IVIG) improves left ventricular ejection fraction (LVEF) in these patients. To examine if this improvement was related to IVIG-induced effects on complement, we also examined complement activation during induction (first week) and maintenance therapy (6 months) with IVIG or placebo. Our main findings were: (1) We found enhanced systemic complement activation involving classic, alternative, as well as terminal pathway in patients with CHF compared with healthy control subjects. (2) Particularly enhanced complement activation was found in coronary sinus, representing venous drainage from the heart. (3) The systemic complement activation was further enhanced during IVIG but not during placebo therapy, particularly during induction therapy. (4) Although IVIG improved LVEF in patients with CHF, the degree of IVIG-mediated complement activation was negatively correlated with this improvement of LVEF.



This study further supports the involvement of innate immunity in the pathogenesis of CHF. Our findings suggest that complement may be added to the list of possible therapeutic targets in CHF and that future studies with specific complement inhibitors may be of interest in this disorder.
Factors influencing participant enrolment in a diabetes prevention program in general practice: lessons from the Sydney diabetes prevention program

The effectiveness of lifestyle interventions in reducing diabetes incidence has been well established. Little is known, however, about factors influencing the reach of diabetes prevention programs. This study examines the predictors of enrolment in the Sydney Diabetes Prevention Program (SDPP), a community-based diabetes prevention program conducted in general practice, New South Wales, Australia from 2008-2011.



SDPP was an effectiveness trial. Participating general practitioners (GPs) from three Divisions of General Practice invited individuals aged 50-65 years without known diabetes to complete the Australian Type 2 Diabetes Risk Assessment tool. Individuals at high risk of diabetes were invited to participate in a lifestyle modification program. A multivariate model using generalized estimating equations to control for clustering of enrolment outcomes by GPs was used to examine independent predictors of enrolment in the program. Predictors included age, gender, indigenous status, region of birth, socio-economic status, family history of diabetes, history of high glucose, use of anti-hypertensive medication, smoking status, fruit and vegetable intake, physical activity level and waist measurement.



Of the 1821 eligible people identified as high risk, one third chose not to enrol in the lifestyle program. In multivariant analysis, physically inactive individuals (OR: 1.48, P = 0.004) and those with a family history of diabetes (OR: 1.67, P = 0.000) and history of high blood glucose levels (OR: 1.48, P = 0.001) were significantly more likely to enrol in the program. However, high risk individuals who smoked (OR: 0.52, P = 0.000), were born in a country with high diabetes risk (OR: 0.52, P = 0.000), were taking blood pressure lowering medications (OR: 0.80, P = 0.040) and consumed little fruit and vegetables (OR: 0.76, P = 0.047) were significantly less likely to take up the program.



Targeted strategies are likely to be needed to engage groups such as smokers and high risk ethnic groups. Further research is required to better understand factors influencing enrolment in diabetes prevention programs in the primary health care setting, both at the GP and individual level.
Audiovisual biofeedback breathing guidance for lung cancer patients receiving radiotherapy: a multi-institutional phase II randomised clinical trial

There is a clear link between irregular breathing and errors in medical imaging and radiation treatment. The audiovisual biofeedback system is an advanced form of respiratory guidance that has previously demonstrated to facilitate regular patient breathing. The clinical benefits of audiovisual biofeedback will be investigated in an upcoming multi-institutional, randomised, and stratified clinical trial recruiting a total of 75 lung cancer patients undergoing radiation therapy. To comprehensively perform a clinical evaluation of the audiovisual biofeedback system, a multi-institutional study will be performed. Our methodological framework will be based on the widely used Technology Acceptance Model, which gives qualitative scales for two specific variables, perceived usefulness and perceived ease of use, which are fundamental determinants for user acceptance. A total of 75 lung cancer patients will be recruited across seven radiation oncology departments across Australia. Patients will be randomised in a 2:1 ratio, with 2/3 of the patients being recruited into the intervention arm and 1/3 in the control arm. 2:1 randomisation is appropriate as within the interventional arm there is a screening procedure where only patients whose breathing is more regular with audiovisual biofeedback will continue to use this system for their imaging and treatment procedures. Patients within the intervention arm whose free breathing is more regular than audiovisual biofeedback in the screen procedure will remain in the intervention arm of the study but their imaging and treatment procedures will be performed without audiovisual biofeedback. Patients will also be stratified by treating institution and for treatment intent (palliative vs. radical) to ensure similar balance in the arms across the sites. Patients and hospital staff operating the audiovisual biofeedback system will complete questionnaires to assess their experience with audiovisual biofeedback. The objectives of this clinical trial is to assess the impact of audiovisual biofeedback on breathing motion, the patient experience and clinical confidence in the system, clinical workflow, treatment margins, and toxicity outcomes. This clinical trial marks an important milestone in breathing guidance studies as it will be the first randomised, controlled trial providing the most comprehensive evaluation of the clinical impact of breathing guidance on cancer radiation therapy to date. This study is powered to determine the impact of AV biofeedback on breathing regularity and medical image quality. Objectives such as determining the indications and contra-indications for the use of AV biofeedback, evaluation of patient experience, radiation toxicity occurrence and severity, and clinician confidence will shed light on the design of future phase III clinical trials. This trial has been registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), its trial ID is ACTRN12613001177741 .
A pilot study of the use of EEG-based synchronized Transcranial Magnetic Stimulation (sTMS) for treatment of Major Depression

Repetitive Transcranial Magnetic Stimulation (rTMS) is an effective treatment for Major Depressive Disorder (MDD), and is based upon delivery of focal high-energy pulses of electromagnetic stimulation. We postulated that delivery of rTMS at the subject's individual alpha frequency (synchronized TMS, or sTMS) would achieve efficacy with lower energy of stimulation. We developed a device that rotates neodymium cylindrical magnets at three locations along the midline above the subject's scalp to impart low-energy, sinusoidal-waveform magnetic brain stimulation over a broad area, and performed this efficacy study.



Fifty-two subjects with MDD were enrolled in a randomized, sham controlled, double-blind treatment study (. Forty-six subjects were included in the final analysis. Most subjects received concurrent antidepressant medications that remained unchanged during the study. Subjects were randomized to three treatment groups: 1) active sTMS with a fixed frequency at the subject's alpha frequency; 2) active sTMS with a random stimulus frequency that varied between 8 Hz and 13 Hz; and, 3) sham sTMS. 20 half-hour sTMS sessions were administered 5 days per week for 4 weeks.



Subjects with either fixed or random frequency active sTMS had statistically significantly greater percentage reduction in depression severity compared to sham (48.5% vs. 19.3%, respectively; p = 0.001). No significant difference was found between fixed and random groups (p = 0.30). No significant side effects were reported.



These results suggest that sTMS may be an effective treatment for MDD.
Validation of a Spanish version of the Revised Fibromyalgia Impact Questionnaire (FIQR)

The Revised version of the Fibromyalgia Impact Questionnaire (FIQR) was published in 2009. The aim of this study was to prepare a Spanish version, and to assess its psychometric properties in a sample of patients with fibromyalgia.



The FIQR was translated into Spanish and administered, along with the FIQ, the Hospital Anxiety Depression Scale (HADS), the 36-Item Short-Form Health Survey (SF-36), and the Brief Pain Inventory (BPI), to 113 Spanish fibromyalgia patients. The administration of the Spanish FIQR was repeated a week later.



The Spanish FIQR had high internal consistency (Cronbach’s α was 0.91 and 0.95 at visits 1 and 2 respectively). The test-retest reliability was good for the FIQR total score and its function and symptoms domains (intraclass correlation coefficient (ICC > 0.70), but modest for the overall impact domain (ICC = 0.51). Statistically significant correlations (p < 0.05) were also found between the FIQR and the FIQ scores, as well as between the FIQR scores and the remaining scales’ scores.



The Spanish version of the FIQR has a good internal consistency and our findings support its validity for assessing fibromyalgia patients. It might be a valid instrument to apply in clinical and investigational grounds.
Low plasma testosterone and elevated carotid intima-media thickness: importance of low-grade inflammation in elderly men.

An inverse correlation between plasma testosterone levels and carotid intima-media thickness (IMT) has been reported in men. We investigated whether this association could be mediated or modified by traditional cardiovascular risk factors as well as inflammatory status.



In the Three-City population-based cohort study, 354 men aged 65 and over had available baseline data on hormones levels and carotid ultrasonography. Plasma concentrations of testosterone (total and bioavailable), estradiol and sex hormone-binding globulin (SHBG), together with cardiovascular risk factors were measured. IMT in plaque-free site and atherosclerotic plaques in the extracranial carotid arteries were determined using a standardized protocol. Multiple linear regression models were used to analyze this association and interaction study.



Analyses with and without adjustment for cardiovascular risk factors showed that carotid IMT was inversely and significantly correlated with total and bioavailable testosterone levels but not with SHBG and estradiol levels. This association depended on C-reactive protein (CRP) levels (p for interaction <0.05). Among men with low-grade inflammation (CRP ≥2 mg/L), mean IMT was higher in subjects with bioavailable testosterone ≤ 3.2 ng/mL than in those with bioavailable testosterone > 3.2 ng/mL (0.76 mm and 0.70 mm respectively, p < 0.01). By contrast, among men with CRP ≤ 2 mg/L, mean IMT was similar in both groups (0.72 mm and 0.71 mm respectively, p = 0.77). Similar results were found for total testosterone although not significant. No association was found between plasma hormones levels and atherosclerotic plaques.



In elderly men, low plasma testosterone is associated with elevated carotid intima-media thickness only in those with low-grade inflammation. Traditional risk factors have no mediator role.
Prediction of response to interferon in patients with chronic active hepatitis C, and evidence that this improves hepatic metabolic function

We sought to ascertain whether response to alpha interferon treatment could be predicted among patients with chronic active hepatitis C, and whether antipyrine clearance estimations would determine changes in liver function with this disease. The patients came from a randomized controlled trial, with patients who were initially untreated eventually being offered interferon treatment. Among 28 patients treated with interferon 18 (64%) responded with normalization of serum aminotransferase levels. Responders were less likely to have acquired hepatitis C by blood transfusion and more likely to have acquired it by intravenous drug abuse (P less than 0.05). All 13 patients with less severe chronic active hepatitis responded to interferon but only 5 of 15 patients with progressive fibrosis or cirrhosis responded (P less than 0.01). During 8-39 (median 19) months of observation of 16 untreated patients, there was a significant fall in antipyrine clearance (Cl-Ap) but no change in serum albumin. Among interferon-treated patients, Cl-Ap improved in 9 of 16 compared with 1 of 14 controls observed for the same time period (P less than 0.02). It is concluded that Cl-Ap is a sensitive test for detecting changes in liver function during chronic hepatitis. Without treatment, deterioration is evident at 18 months in 50% of patients with chronic active hepatitis C. Conversely, normalization of serum aminotransferase levels by interferon is associated with improvement of Cl-Ap.(ABSTRACT TRUNCATED AT 250 WORDS)