nils-herrmann/clean_scirepeval huggingface dataset:
Long-term risk of venous thrombosis after stopping anticoagulants for a first unprovoked event: A multi-national cohort.

Choosing short-term (3-6 months) or indefinite anticoagulation after a first unprovoked venous thromboembolic event (VTE) is a common and difficult clinical decision. The long-term absolute risk of recurrent VTE after a first unprovoked VTE, in all patients and sub-groups, is not well established, hindering decision making.



We conducted a multi-center multi-national prospective cohort study in first unprovoked VTE patients to establish the long-term risk of recurrent VTE after short-term anticoagulation in first unprovoked VTE patients (and sub-groups).We followed patients for symptomatic suspected VTE off of OAT. Suspected recurrent VTE was investigated with reference to baseline imaging and then independently and blindly adjudicated.



We recruited 663 participants between October, 2001 and March 2006 with the last follow-up in April 2014. During a mean 5.0 years of follow-up, 165/663 suspected VTE (in 408 patients) were adjudicated as recurrent VTE resulting in an annualized risk of recurrent VTE of 5.0% (95% CI: 4.2-5.8%) with a cumulative risk of 29.6% at 8 years. Men had a 7.6% (95% CI: 6.3-9.2%) annual risk of recurrent VTE. High risk women (2 or more HERDOO2 points; see text) had an annual risk of recurrent VTE of 5.9% (95% CI: 4.2-8.1%). Low risk women (1 or 0 HERDOO2 points) had 1.1% (95% CI: 0.6-2.0%) annual risk of recurrent VTE with a cumulative risk of 8.7% at 8 years.



Men and high risk women with unprovoked VTE should be considered for long-term anticoagulant therapy given a high risk of recurrent VTE after long-term follow-up. Women with a low HERDOO2 score may be able to safely discontinue anticoagulants.



This study was funded by the Canadian Institutes of Health Research (Grant # MOP 64319) and Heart and Stroke Foundation of Ontario (Grant
Validation of a screening instrument for exposure to violence in African American children.

To provide concurrent validity data for the KID-SAVE as a screening instrument for exposure to violence in African American children, to explore demographic differences in KID-SAVE scores, and to provide preliminary reliability data on a parent version of the KID-SAVE.



Questionnaire data were collected regarding exposure to violence, children's behavior and symptoms, and family aggression. A sample of 182 children and their parents participated.



Both parent and child report of violence exposure was significantly related to the child's psychological adjustment as endorsed by both parents and children. Also, significant relationships were obtained between parent report of their child's exposure to violence and the presence of family violence.



The KID-SAVE appears to be a promising instrument for the assessment of exposure to violence, specifically in African American children, and may be applicable in a variety of clinical settings.
Thought disorder in schizophrenia. Testing models through confirmatory factor analysis

Theoretical and empirical models of thought disorder (ThD) were tested through Confirmatory factor analysis (CFA). A sample of 253 DSM-III-R acute schizophrenic patients consecutively admitted was studied. A semistructured interview for schizophrenia was used for diagnosis, and ThD was assessed by means of the Thought, Language, and Communication scale (TLC). Nine ThD models comprising the 18 symptoms of the TLC were tested (ranging from a null model to a six-factor model). The six-dimension model achieved the best fit to the data, although no perfect fit was found. ThD dimensions included in this model were Disorganization, Negative, Idiosyncratic, Semantic, Attentional, and Referential dimensions. The TLC was close to capture adequately these underlying constructs. The Disorganization and the Negative dimensions received more validity on conceptual and psychometric grounds than the remaining dimensions. Thought Disorder multidimensional models fitted the data better than one-dimension models. Thought Disorder dimensions would be potential markers for biological, neurophysiological, and neuropsychological studies of schizophrenic disorder.
Feasibility of MicroRNAs as Biomarkers for Barrett's Esophagus Progression: A Pilot Cross-Sectional, Phase 2 Biomarker Study

Risk stratification of Barrett's esophagus (BE) using biomarkers remains an important goal. We evaluated feasibility and clinical accuracy of novel microRNA (miRNA) biomarkers for prediction of BE dysplasia.Paired fresh-frozen and hematoxylin/eosin specimens from a prospective tissue repository where only biopsies with the lesion of interest (i.e., intestinal metaplasia (IM) or high-grade dysplasia (HGD)/esophageal adenocarcinoma (EAC)) occupying >50% of biopsy area were included. Tissue miRNA expression was determined by microarrays and validated by quantitative reverse transcription-PCR (qRT-PCR). Three groups were compared—group A, IM tissues from BE patients without dysplasia; group B, IM tissues from group C patients; and group C, dysplastic tissues from BE patients with HGD/Overall, 22 BE patients, 11 with and without dysplasia (mean age 64±8.2 and 63±11.6 years, respectively, all Caucasian males) were evaluated. Nine miRNAs were identified by high-throughout analysis (miR-15b, -21, -192, -205, 486-5p, -584, -1246, let-7a, and -7d) and qRT-PCR confirmed expression of miR-15b, -21, 486-5p, and let-7a. Two of 4 miRNAs (miR-145 and -203, but not -196a and -375) previously described in BE patients also exhibited differential expression. Sensitivity and specificity of miRNAs for HGD/EAC were miR-15b: 87 and 80%, miR-21: 93 and 70%, miR-203: 87 and 90%, miR-486-5p: 82 and 55%, and miR-let-7a: 88 and 70%. MiRNA-15b, -21, and -203 exhibited field effects (i.e., groups A and B tissues while histologically similar yet exhibited different miRNA This pilot study demonstrates feasibility of miRNAs to discriminate BE patients with and without dysplasia with reasonable clinical accuracy. However, the specific miRNAs need to be evaluated further in future prospective trials.
Evaluation of intravenous immunoglobulin as an agent to lower allosensitization and improve transplantation in highly sensitized adult patients with end-stage renal disease: report of the NIH IG02 trial.

Reported are the reduction of anti-HLA antibody levels and improvement of transplant rates by intravenous immunoglobulin (IVIG) in a randomized, double-blind, placebo-controlled clinical trial. Between 1997 and 2000, a total of 101 adult patients with ESRD who were highly sensitized to HLA antigens (panel reactive antibody [PRA] > or =50% monthly for 3 mo) enrolled onto an NIH-sponsored trial (IG02). Patients received IVIG or placebo. Subjects received IVIG 2 g/kg monthly for 4 mo or an equivalent volume of placebo with additional infusions at 12 and 24 mo after entry if not transplanted. If transplanted, additional infusions were given monthly for 4 mo. Baseline PRA levels were similar in both groups. However, IVIG significantly reduced PRA levels in study subjects compared with placebo. Sixteen IVIG patients (35%) and eight placebo patients (17%) were transplanted. Rejection episodes occurred in 9 of 17 IVIG and 1 of 10 placebo subjects. Seven graft failures occurred (four IVIG, three placebo) among adherent patients with similar 2-yr graft survival rates (80% IVIG, 75% placebo). With a median follow-up of 2 yr after transplant, the viable transplants functioned normally with a mean +/- SEM serum creatinine of 1.68 +/- 0.28 for IVIG versus 1.28 +/- 0.13 mg/dl for placebo. Adverse events rates were similar in both groups. We conclude that IVIG is better than placebo in reducing anti-HLA antibody levels and improving transplantation rates in highly sensitized patients with ESRD. Transplant rates for highly sensitized patients with ESRD awaiting kidney transplants are improved with IVIG therapy.
Deep brain stimulation plus best medical therapy versus best medical therapy alone for advanced Parkinson's disease (PD SURG trial): a randomised, open-label trial

Surgical intervention for advanced Parkinson's disease is an option if medical therapy fails to control symptoms adequately. We aimed to assess whether surgery and best medical therapy improved self-reported quality of life more than best medical therapy alone in patients with advanced Parkinson's disease.



The PD SURG trial is an ongoing randomised, open-label trial. At 13 neurosurgical centres in the UK, between November, 2000, and December, 2006, patients with Parkinson's disease that was not adequately controlled by medical therapy were randomly assigned by use of a computerised minimisation procedure to immediate surgery (lesioning or deep brain stimulation at the discretion of the local clinician) and best medical therapy or to best medical therapy alone. Patients were analysed in the treatment group to which they were randomised, irrespective of whether they received their allocated treatment. The primary endpoint was patient self-reported quality of life on the 39-item Parkinson's disease questionnaire (PDQ-39). Changes between baseline and 1 year were compared by use of t tests. 
366 patients were randomly assigned to receive immediate surgery and best medical therapy (183) or best medical therapy alone (183). All patients who had surgery had deep brain stimulation. At 1 year, the mean improvement in PDQ-39 summary index score compared with baseline was 5.0 points in the surgery group and 0.3 points in the medical therapy group (difference -4.7, 95% CI -7.6 to -1.8; p=0.001); the difference in mean change in PDQ-39 score in the mobility domain between the surgery group and the best medical therapy group was -8.9 (95% CI -13.8 to -4.0; p=0.0004), in the activities of daily living domain was -12.4 (-17.3 to -7.5; p<0.0001), and in the bodily discomfort domain was -7.5 (-12.6 to -2.4; p=0.004). Differences between groups in all other domains of the PDQ-39 were not significant. 36 (19%) patients had serious surgery-related adverse events; there were no suicides but there was one procedure-related death. 20 patients in the surgery group and 13 in the best medical therapy group had serious adverse events related to Parkinson's disease and drug treatment.



At 1 year, surgery and best medical therapy improved patient self-reported quality of life more than best medical therapy alone in patients with advanced Parkinson's disease. These differences are clinically meaningful, but surgery is not without risk and targeting of patients most likely to benefit might be warranted.
Validation of a track repeating algorithm for intensity modulated proton therapy: clinical cases study.

Monte Carlo (MC) methods are acknowledged as the most accurate technique to calculate dose distributions. However, due its lengthy calculation times, they are difficult to utilize in the clinic or for large retrospective studies. Track-repeating algorithms, based on MC-generated particle track data in water, accelerate dose calculations substantially, while essentially preserving the accuracy of MC. In this study, we present the validation of an efficient dose calculation algorithm for intensity modulated proton therapy, the fast dose calculator (FDC), based on a track-repeating technique. We validated the FDC algorithm for 23 patients, which included 7 brain, 6 head-and-neck, 5 lung, 1 spine, 1 pelvis and 3 prostate cases. For validation, we compared FDC-generated dose distributions with those from a full-fledged Monte Carlo based on GEANT4 (G4). We compared dose-volume-histograms, 3D-gamma-indices and analyzed a series of dosimetric indices. More than 99% of the voxels in the voxelized phantoms describing the patients have a gamma-index smaller than unity for the 2%/2 mm criteria. In addition the difference relative to the prescribed dose between the dosimetric indices calculated with FDC and G4 is less than 1%. FDC reduces the calculation times from 5 ms per proton to around 5 μs.
A comparison of the health status after percutaneous coronary intervention at a hospital with and without on-site cardiac surgical backup: a randomized trial in nonemergent patients.

Prospective randomized trials comparing the coronary artery disease-related health status outcomes (changes in symptom grade, physical functional capacity and health-related quality of life) after percutaneous coronary intervention at hospitals with and without on-site cardiac surgical backup have not been reported earlier.



We randomly assigned 609 consecutive patients fulfilling pre-specified procedural low-risk criteria to undergo percutaneous coronary intervention at either a community hospital without or a regional hospital with on-site surgical backup. Five hundred and seventy-six patients completed the health status evaluation at baseline and at 6 months follow-up.



At baseline, 91.4% had symptoms, and the mean (standard deviation) Canadian Cardiovascular Society's classification was 2.5 (0.9). The procedural success rates and the changes in health status measures were similar at the two hospitals. Overall there was a substantial relief of symptoms with a reduction in Canadian Cardiovascular Society's classification of 1.9 (1.2), increase in exercise time [1.4 (1.9) min] and reduction in use of antianginal drugs [0.6 (0.9) less drugs] at follow-up compared with baseline (all P<0.001). Health-related quality of life was evaluated with the Short-Form 36 health survey. There were significant and similar improvements in nearly all multi-item and summary scores from baseline to follow-up at the two hospitals. The largest improvements were seen in items related to physical functioning [overall change in Physical Component Score from baseline to follow-up 6.9 (9.1) points, P<0.001] and lowest in the mental health domains [change in Mental Component Score 3.3 (10.7) points, P<0.001].



This study shows that a substantial and comparable gain in coronary artery disease-related health status can be achieved at hospitals both with and without surgical backup.
Training improves muscle oxidative capacity and oxygenation recovery kinetics in patients with chronic obstructive pulmonary disease

We studied 21 patients with chronic obstructive pulmonary disease aged [mean (SD)] 63 (10) years, with a mean forced expiratory volume in 1 s of 40 (6)% and a peak oxygen uptake of 67 (11)% of predicted values. Patients trained for 6 weeks on a cycle ergometer at high work-rates (WR). Near-infrared spectroscopy was used to obtain the time-constant of the deoxygenation recovery signal (τHbO2) during three constant WR exercise tests, one below and two above the lactic acidosis threshold (θL). Glycolytic and oxidative enzymes and lactate concentrations were assessed in muscle biopsies. The τHbO2 decreased significantly in all three constant WR tests: –18 (24)s, –20 (23) s and –13 (22) s, respectively. Endurance time increased in the higher WR tests, by 5.7 (4.8) min and 3.6 (2.7) min, respectively. The activity of citrate-synthase (CS) and creatine-kinase changed significantly from 20 (10) to 30 (13) µmol·min–1·g–1 and from 3.825 (950) to 3.402 (526) µmol·min–1·g–1, respectively. Training also improved significantly the mean response time of the on-transient of oxygen uptake (τ'V˙O2) of the below-θL test. We found significant correlations between changes in CS and changes in τHbO2, τ'V˙O2 and endurance time. We conclude that leg training accelerates the speed of re-oxygenation of the vastus lateralis muscle after exercise. This improvement is correlated to changes in the oxidative enzymes.
Steady-state pharmacokinetic comparison of generic and branded formulations of stavudine, lamivudine and nevirapine in HIV-infected Ugandan adults.

We aimed to compare the steady-state pharmacokinetic parameters and tolerability of Triomune 40 (stavudine 40 mg, lamivudine 150 mg and nevirapine 200 mg) and branded formulations of these drugs in HIV-infected Ugandans.



This includes a randomized, open-label, cross-over study of HIV-infected patients stable on therapy for 1 month. Patients were randomized to generic or branded formulation. Plasma pharmacokinetics were assessed after 1 month. The following day, alternate formulation was administered, and 1 month later, drug pharmacokinetics were re-assessed. Plasma pharmacokinetics were determined using HPLC-UV detection. Similarity between steady-state pharmacokinetic parameters was assessed using the US Food and Drug Administration standards for bioequivalency testing. Tolerability was assessed using questionnaires.



Sixteen (10 females) patients completed the study. Median (IQR) age, weight and CD4 count were 37 (33.7-40) years, 65 (63.4-66) kg and 292 (220.7-344.5) cells/mm(3), respectively. All patients received co-trimoxazole. The geometric mean ratio (90% CI) for stavudine, lamivudine and nevirapine was 0.92 (0.78-1.08), 1.11 (0.95-1.30) and 0.84 (0.64-1.11), respectively, for C(max), and 0.83 (0.70-0.97), 1.06 (0.94-1.20) and 0.88 (0.71-1.10), respectively, for AUC. Stavudine plasma concentrations were significantly lower for the generic formulation. Pharmacokinetic parameter inter-individual variability ranged from 29% to 99%. There were no differences in tolerability for the two formulations.



Pharmacokinetic profiles of generic and branded drugs were similar. Differences particularly with regard to stavudine were demonstrated. Surveillance of the quality of generic antiretroviral drugs in the target populations is needed. Capacity building for pharmacokinetic research in resource-limited settings is a priority.
Increase in urinary leukotriene LTE4 levels in acute asthma: correlation with airflow limitation.

Leukotrienes play a key role in the pathophysiology of chronic asthma. Activation of leukotriene pathways is accompanied by rises in detectable urinary levels of leukotriene E4 (LTE4). The relationship between urinary LTE4 levels and factors associated with acute asthma has not been determined.



Adults aged 15-54 years presenting with moderate to severe acute asthma were evaluated at emergency departments in 16 US sites. Forced expiratory volume in 1 second (FEV1) was measured during the first 60 minutes after arrival and at specified times until discharge or admission. Urine samples for measurement of LTE4 levels were obtained either on arrival at the study site and/or before discharge. Patients were seen 2 weeks later for follow up, at which time repeat FEV1 measurements and urine samples for LTE4 were obtained.



One hundred and eighty four patients were evaluated; LTE4 results from both the acute and follow up periods were available for analysis in 146. Urinary LTE4 levels were increased during asthma exacerbations compared with levels obtained 2 weeks later (geometric means 111.7 and 75.6 pg/mg creatinine, respectively, mean percentage change -32.3; 95% confidence interval (CI) for the mean percentage change -39.6 to -24.3, p<0.001). The correlation between improvement in FEV1 and decline in LTE4 over the 2 week interval was significant (p<0.001, r=0.43).



Activation of leukotriene pathways in acute asthma is correlated with the degree of airflow obstruction, and resolution of the asthma exacerbation is associated with a reduction in leukotriene levels.
Fat intake at midlife and cognitive impairment later in life: a population-based CAIDE study.

To investigate the association of midlife dietary fat intake to cognitive performance, and to the occurrence of clinical mild cognitive impairment (MCI) later in life in a non-demented population.



A longitudinal population-based study.



Populations of Kuopio and Joensuu, Eastern Finland.



Participants of the CAIDE study were derived from random, population-based samples studied at midlife (1972, 1977, 1982 or 1987). After an average follow-up of 21 years, a total of 1449 (72%) individuals aged 65-80 years participated in the re-examination in 1998. Altogether 82 (5.7%) people were diagnosed as having MCI. Dietary information was collected with a structured questionnaire and an interview at midlife.



MCI, global cognitive and executive functions, episodic, semantic and prospective memory and psychomotor speed.



Abundant saturated fat (SFA) intake from milk products and spreads at midlife was associated with poorer global cognitive function and prospective memory and with an increased risk of MCI (OR 2.36, 95% CI 1.17-4.74) after adjusting for demographic and vascular factors, other fats and ApoE. On the contrary, high intake of polyunsaturated fatty acids (PUFA) was associated with better semantic memory. Also frequent fish consumption was associated with better global cognitive function and semantic memory. Further, higher PUFA-SFA ratio was associated with better psychomotor speed and executive function.



Our data suggests that dietary fat intake at midlife affects cognitive performance and occurrence of MCI later in life. The impact of dietary interventions needs to be tested in clinical trials.
Evaluation of multiplex real-time PCR for detection of Haemophilus ducreyi, Treponema pallidum, herpes simplex virus type 1 and 2 in the diagnosis of genital ulcer disease in the Rakai District, Uganda.

To develop a real-time PCR assay that reliably and accurately detects the predominant sexually transmitted aetiological agents of genital ulcer disease (GUD) (Haemophilus ducreyi, Treponema pallidum and herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2)) and to assess the use of real-time PCR diagnostic testing in a rural African field site.



Two multiplex real-time PCR reactions were used to detect H ducreyi/and HSV-1/HSV-2 in ulcer swabs from 100 people with symptomatic genital ulcers in rural Rakai, Uganda. Results were compared with syphilis, HSV-1 and HSV-2 serology.



Of 100 GUD samples analysed from 43 HIV positive and 57 HIV negative individuals, 71% were positive for one or more sexually transmitted infection (STI) pathogens by real-time PCR (61% for HSV-2, 5% for T pallidum, 3% for HSV-1, 1% for H ducreyi and 1% for dual H ducreyi/HSV-2). The frequency of HSV in genital ulcers was 56% (32/57) in HIV negative individuals and 77% (33/43) in HIV positive individuals (p = 0.037). Assay reproducibility was evaluated by repeat PCR testing in the USA with 96% agreement (kappa = 0.85).



STI pathogens were detected in the majority of GUD swab samples from symptomatic patients in Rakai, Uganda, by real-time PCR. HSV-2 was the predominant cause of genital ulcers. Real-time PCR technology can provide sensitive, rapid and reproducible evaluation of GUD aetiology in a resource-limited setting.
Robust estimation of protein expression ratios with lysate microarray technology

The protein lysate microarray is a developing proteomic technology for measuring protein expression levels in a large number of biological samples simultaneously. A challenge for accurate quantification is the relatively narrow dynamic range associated with the commonly used chromogenic signal detection system. To facilitate accurate measurement of the relative expression levels, each sample is serially diluted and each diluted version is spotted on a nitrocellulose-coated slide in triplicate. Thus, each sample yields multiple measurements in different dynamic ranges of the detection system. This study aims to develop suitable algorithms that yield accurate representations of the relative expression levels in different samples from multiple data points.



We evaluated two algorithms for estimating relative protein expression in different samples on the lysate microarray by means of a cross-validation procedure. For this purpose as well as for quality control we designed a 1440-spot lysate microarray containing 80 identical samples of purified bovine serum albumin, printed in triplicate with six 2-fold dilutions. Our analysis showed that the algorithm based on a robust least squares estimator provided the most accurate quantification of the protein lysate microarray data. We also demonstrated our methods by estimating relative expression levels of p53 and p21 in either p53(+/+) or p53(-/-) HCT116 colon cancer cells after two drug treatments and their combinations on another lysate microarray.