nils-herrmann/clean_scirepeval huggingface dataset:
Open-label, phase I dose-escalation study of sodium selenate, a novel activator of PP2A, in patients with castration-resistant prostate cancer

Angiogenesis is fundamental to the progression of many solid tumours including prostate cancer. Sodium selenate is a small, water-soluble, orally bioavailable activator of PP2A phosphatase with anti-angiogenic properties.This was a dose-escalation phase I study in men with asymptomatic, chemotherapy-naïve, castration-resistant prostate cancer. The primary objective was to determine the maximum tolerated dose (MTD). Secondary objectives included establishing the safety, tolerability and pharmacokinetic profile.A total of 19 patients were enrolled. The MTD was 60 mg per day. Dose-limiting toxicity (fatigue and diarrhoea) was observed at 90 mg per day. The most frequently reported treatment-related adverse events across all treatment cohorts were nausea, diarrhoea, fatigue, muscle spasms, alopecia and nail disorders. No grade 4 toxicities were observed and there were no deaths on study. Linear pharmacokinetics was observed. One patient had a PSA response >50%. Median time to PSA progression (for non-responders) was 14.2 weeks. Mean PSA doubling time increased during the main treatment phase from 2.18 months before trial to 3.85 months.Sodium selenate is well tolerated at a dose of 60 mg per day with modest single-agent efficacy similar to other anti-angiogenic agents. Further trials in combination with conventional cytotoxic regimens are warranted.
Withdrawal of dopamine agonist therapy in prolactinomas: In which patients and when?

The aim of the study was to assess the effect of dopamine agonist (DA) withdrawal, the current recurrence rate of hyperprolactinemia, and possible factors that predict recurrence in patients with prolactinoma. We evaluated DA withdrawal in 67 patients with prolactinoma (50 female/17 male) who received DA treatment for at least 2 years and showed normalization of prolactin (PRL) levels and tumor disappearance or ≥50 % tumor shrinkage, retrospectively. Accordingly, patients were divided into two groups as remission and recurrence groups, and factors that predict recurrence were evaluated. The overall remission rate was 46 %; the remission ratios were 65 % in microprolactinomas and 36 % in macroprolactinomas. Remission rates were 39 % in the bromocriptine withdrawal group and 55 % in the cabergoline withdrawal group. The maximum tumor diameter and baseline PRL levels were significantly higher in the recurrence group (p = 0.001 and p = 0.003, respectively). The mean duration of DA therapy was significantly longer in the remission group (88.7 ± 48.1 and 66.7 ± 30.4 months, respectively, p = 0.026).The mean time to recurrence was 5.3 ± 3.2 months. The mean PRL levels at recurrence time were significantly lower than baseline PRL levels (p = 0.001). The most important predictors of recurrence were maximum tumor diameter and baseline PRL levels in this study. The remission rate in our study group was higher, which was thought to be associated with the longer duration of DA treatment and that our patients were selected according to certain criteria. Despite these positive results, close monitoring is necessary for detection of early and late recurrence, especially within the first year after DA withdrawal.
Study protocol: Transition from localized low back pain to chronic widespread pain in general practice: Identification of risk factors, preventive factors and key elements for treatment – A cohort study

Chronic localized pain syndromes, especially chronic low back pain (CLBP), are common reasons for consultation in general practice. In some cases chronic localized pain syndromes can appear in combination with chronic widespread pain (CWP). Numerous studies have shown a strong association between CWP and several physical and psychological factors. These studies are population-based cross-sectional and do not allow for assessing chronology. There are very few prospective studies that explore the predictors for the onset of CWP, where the main focus is identifying risk factors for the CWP incidence. Until now there have been no studies focusing on preventive factors keeping patients from developing CWP. Our aim is to perform a cross sectional study on the epidemiology of CLBP and CWP in general practice and to look for distinctive features regarding resources like resilience, self-efficacy and coping strategies. A subsequent cohort study is designed to identify the risk and protective factors of pain generalization (development of CWP) in primary care for CLBP patients.



Fifty-nine general practitioners recruit consecutively, during a 5 month period, all patients who are consulting their family doctor because of chronic low back pain (where the pain is lasted for 3 months). Patients are asked to fill out a questionnaire on pain anamnesis, pain-perception, co-morbidities, therapy course, medication, socio demographic data and psychosomatic symptoms. We assess resilience, coping resources, stress management and self-efficacy as potential protective factors for pain generalization. Furthermore, we raise risk factors for pain generalization like anxiety, depression, trauma and critical life events. During a twelve months follow up period a cohort of CLBP patients without CWP will be screened on a regular basis (3 monthly) for pain generalization (outcome: incident CWP).



This cohort study will be the largest study which prospectively analyzes predictors for transition from CLBP to CWP in primary care setting. In contrast to the typically researched risk factors, which increase the probability of pain generalization, this study also focus intensively on protective factors, which decrease the probability of pain generalization.
Effects of Aprepitant on the Pharmacokinetics of Controlled-Release Oral Oxycodone in Cancer Patients

Oxycodone is a µ-opioid receptor agonist widely used in the treatment of cancer pain. The predominant metabolic pathway of oxycodone is CYP3A4-mediated N-demethylation to noroxycodone, while a minor proportion undergoes 3-O-demethylation to oxymorphone by CYP2D6. The aim of this study was to investigate the effects of the mild CYP3A4 inhibitor aprepitant on the pharmacokinetics of orally administered controlled-release (CR) oxycodone.



This study design was an open-label, single-sequence with two phases in cancer patients with pain who continued to be administered orally with multiple doses of CR oxycodone every 8 or 12 hours. Plasma concentration of oxycodone and its metabolites were measured up to 8 hours after administration as follows: on day 1, CR oxycodone was administered alone; on day 2, CR oxycodone was administered with aprepitant (125 mg, at the same time of oxycodone dosing in the morning). The steady-state trough concentrations (Css) were measured from day 1 to day 3.



Aprepitant increased the area under the plasma concentration-time curve (AUC0-8) of oxycodone by 25% (p<0.001) and of oxymorphone by 34% (p<0.001), as well as decreased the AUC0-8 of noroxycodone by 14% (p<0.001). Moreover, aprepitant increased Css of oxycodone by 57% (p = 0.001) and of oxymorphone by 36% (p<0.001) and decreased Css of noroxycodone by 24% (p = 0.02) at day 3 compared to day 1.



The clinical use of aprepitant in patients receiving multiple doses of CR oxycodone for cancer pain significantly altered plasma concentration levels, but would not appear to need modification of the CR oxycodone dose.
Results of 101 aneurysms treated with polyglycolic/polylactic acid microfilament nexus coils compared with historical controls treated with standard coils.

Polyglycolic/polylactic acid (PGLA) addition to bare platinum coils is intended to reduce the reopening rate of coiled intracranial aneurysms. Nexus coils are standard complex platinum coils with interwoven PGLA microfilament threads. We present the clinical results of 101 intracranial aneurysms treated with Nexus coils.



Results of coiling of 101 aneurysms treated with Nexus coils were compared with our results of coiling of 120 aneurysms with Guglielmi detachable coils (GDC 10) and 115 with Trufill coils treated between May 2003 and December 2004 with the same treatment protocol. Rate of complications, mean aneurysmal volume, packing attenuation, incomplete aneurysmal occlusion at 6 months, and rates of retreatment were compared.



Initial occlusion in aneurysms treated with Nexus coils was (near) complete in 97 aneurysms and incomplete in 4 aneurysms. There were no permanent procedural complications (0/95 patients, 0%; 97.5% CI, 0.0% to 3.3%). Mean aneurysmal volume was 180.2 mm(3) (range, 5-1624 mm(3)). Mean packing was 19.4% (range, 7.5% to 38.9%). Six months' angiographic follow-up in 87 of 101 aneurysms showed incomplete occlusion in 14 (16%), and 12 (14%) of those had additional coiling. Mean packing of 19.4% of Nexus coils was significantly lower than 22.9% for GDC 10 and 29.7% for Trufill coils. Other clinical results were not significantly different.



In this series, PGLA microfilament Nexus coils were safe to use with clinical results comparable with those of standard platinum coils. This study gives additional evidence of the lack of beneficial effect of PGLA addition to reduce the reopening rate of coiled intracranial aneurysms.
Green tea extract as a treatment for patients with wild-type transthyretin amyloidosis: an observational study

Causative treatment of patients with wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM) is lacking. Recent reports indicate the potential use of epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea, to inhibit amyloid fibril formation. We sought to investigate changes of cardiac function and morphology in patients with wtATTR-CM after consumption of green tea extract (GTE).



Twenty-five male patients (71 [64; 80] years) with wtATTR-CM were submitted to clinical examination, echocardiography, cardiac magnetic resonance imaging (cMRI) (n=14), and laboratory testing before and after daily consumption of GTE capsules containing 600 mg epigallocatechin-3-gallate for at least 12 months.



A significant decrease of left ventricular (LV) myocardial mass by 6% (196 [100; 247] vs 180 [85; 237] g; P=0.03) by cMRI and total cholesterol by 8.4% (191 [118; 267] vs 173 [106; 287] mg/dL; P=0.006) was observed after a 1-year period of GTE consumption. LV ejection fraction by cMRI (53% [33%; 69%] vs 54% [28%; 71%]; P=0.75), LV wall thickness (17 [13; 21] vs 18 [14; 25] mm; ), and mitral annular plane systolic excursion (10 [5; 23] vs 8 [4; 13] mm; P=0.3) by echocardiography remained unchanged.



This study supports LV mass stabilization in patients with wtATTR-CM consuming GTE potentially indicating amyloid fibril reduction.
Monitoring diastolic dysfunction using a simplified algorithm in patients undergoing off-pump coronary artery bypass grafting surgery

Left ventricle diastolic dysfunction (LVDD) is gaining importance as useful marker of mortality and morbidity in cardiac surgical patients. Different algorithms have been proposed for the intraoperative grading of DD. Knowledge of the particular grade of DD has clinical implications with the potential to modify therapy, but there is a paucity of literature on the role of diastolic function evaluation during off-pump coronary artery bypass grafting (OPCABG) surgery.



The aim of this study was to monitor changes in LVDD using simplified algorithm proposed by Swaminathan et al. in patients undergoing OPCABG.



The study was conducted in a tertiary care level hospital; this was a prospective, observational study.



Fifty consecutive patients undergoing OPCABG were enrolled. Hemodynamic and echocardiographic parameters were measured at 6 stages in every patient namely after anesthetic induction (baseline), during left internal mammary artery (LIMA) to left anterior descending (LAD) grafting (LIMA → LAD), saphenous vein graft (SVG) to obtuse marginal (OM) grafting (SVG → OM), SVG to posterior descending artery (PDA) grafting (SVG → PDA), during proximal anastomosis of SVG to aorta, and postprotamine. The patients were classified in grades of LVDD as per simplified algorithm proposed by Swaminathan et al. using only intraoperatively measured E and E'.



The success rate of measurement and classification of LVDD was 98.92% (277 out of 280 measurements). The grades of LVDD varied significantly as per surgical steps with maximum downgrading occurring during OM and LAD grafting. During OM grafting, none of the patients had normal diastolic function while 29% of patients exhibited restrictive pattern (Grade 3 LVDD). Patients with normal baseline LV diastolic function also exhibited downgrading during OM and LAD grafting. Postprotamine, 37% of patients with normal baseline diastolic function continued to exhibit some degree of DD.



The LVDD changes dynamically during various stages of OPCABG, which can be successfully monitored with simplified algorithm.
Prospective validation of HLA-DRB1*07:01 allele carriage as a predictive risk factor for lapatinib-induced liver injury.

Liver injury is a serious adverse event leading to permanent discontinuation of lapatinib in affected patients. This study aimed to validate previously associated major histocompatibility complex (MHC) variants as predictors of risk of liver injury by using a large, randomized, placebo-controlled trial of lapatinib in human epidermal growth factor receptor 2-positive, early-stage breast cancer (Tykerb Evaluation After Chemotherapy [TEACH]: Lapatinib Versus Placebo In Women With Early-Stage Breast Cancer).



The frequency of ALT elevation cases was compared among four MHC variants in 1,194 patients randomly assigned to lapatinib. Cumulative ALT elevation time courses during treatment were also compared between carriers and noncarriers of specified MHC variants.



In lapatinib-treated patients, there was a significant difference in ALT case incidence between HLA carriers and noncarriers. The highly correlated alleles HLA-DRB1*07:01 and HLA-DQA1*02:01 (study frequency, 22.4%) were associated with ALT elevation (odds ratio, 14) between cases (n = 37) and controls (n = 1,071). These associations strengthened at higher ALT elevation thresholds and in Hy's Law cases. In lapatinib-treated patients, the overall risk for National Cancer Institute-Common Terminology Criteria for Adverse Events grade 3 ALT elevation (> 5× upper limit of normal) was 2.1%; HLA allele carriers had an increased risk of 7.7%; in noncarriers, risk was reduced to 0.5%, comparable to ALT elevation for all patients receiving placebo. The increase in ALT case incidence in the lapatinib arm showed no evidence of plateau during 1 year of lapatinib treatment.



These results validate HLA-DRB1*07:01 allele carriage as a predictor of increased risk of lapatinib-induced liver injury and implicate an immune pathology. The HLA association could support clinical management of patients experiencing hepatotoxicity during lapatinib treatment.
A comparison of intranasal fentanyl spray with oral transmucosal fentanyl citrate for the treatment of breakthrough cancer pain: an open-label, randomised, crossover trial.

The efficacy of intranasal fentanyl spray (INFS) was compared with that of oral transmucosal fentanyl citrate (OTFC) for the relief of cancer-related breakthrough pain (BTP) in an open-label, crossover trial.



Adult cancer patients receiving stable background opioid treatment and experiencing BTP episodes were recruited from 44 study centres in seven European countries (Austria, France, Germany, Italy, Poland, Spain and the United Kingdom); of the 196 patients enrolled, 139 were randomised to receive INFS followed by OTFC, or vice versa. Patients were titrated to an effective dose of one agent (50, 100 or 200 microg INFS; 200, 400, 600, 800, 1200 or 1600 microg OTFC) to treat six BTP episodes, then titration and treatment were repeated with the other agent. The primary outcome was patient-recorded time to onset of 'meaningful' pain relief. Secondary outcomes included pain intensity difference (PID) at 10 and 30 minutes (PID(10), PID(30)), sum of PID at 15 and 60 minutes (SPID(0-15), SPID(0-60)), ease of administration, treatment preference and relationship between background opioid dose and effective INFS dose. Additional outcome measures included proportions of episodes with > or =33% and > or =50% pain intensity (PI) reduction, and PID at additional time points.



Among the intention-to-treat population (n = 139), median time to onset of 'meaningful' pain relief was 11 minutes with INFS versus 16 minutes with OTFC; 65.7% of patients attained faster time to 'meaningful' pain-relief onset with INFS (p < 0.001). PID was statistically significantly greater for INFS than OTFC from 5 minutes post-dosing. Significantly more INFS-treated breakthrough pain episodes achieved clinically important pain relief (> or =33% and > or =50% PI reduction) up to 30 minutes post-dosing. The proportions of episodes treated with INFS and OTFC achieving a PI reduction of > or =33% at 5 minutes were 25.3% versus 6.8% (p < 0.001), and at 10 minutes were 51.0% versus 23.6% (p < 0.001), respectively; the proportions of episodes treated with INFS and OTFC achieving a > or =50% PI reduction at 5 minutes were 12.8% versus 2.1% (p < 0.001), and at 10 minutes were 36.9% versus 9.7% (p < 0.001), respectively. Higher SPID(0-15) and SPID(0-60) scores were achieved with INFS (p < 0.001). More patients preferred INFS than OTFC (p < 0.001) and more patients found it very easy/easy to use. Both treatments were well tolerated. In the safety population (n = 139), 56.8% (n = 79) of patients experienced > or =1 AE during the trial. The only AE that occurred in > or =5% of patients in either treatment group was nausea. Among those patients who experienced serious AEs (13.7%, n = 19), none were considered to be related to either study medication. There was a weak correlation between effective INFS doses and background opioid doses.



In this open-label, randomised, crossover trial, significantly more patients attained faster 'meaningful' pain relief with INFS than OTFC, and more patients preferred INFS to OTFC.
Social isolation and depression predict 12-month outcomes in the "waiting for a new heart study".

Identification of modifiable psychosocial characteristics related to survival of heart transplant (HTx) candidates is needed to prevent clinical deterioration and improve prognosis.



A multi-site, prospective study was conducted with 318 HTx candidates (18% female, 82% male; 53 +/- 11 years of age) newly listed at 17 hospitals in Germany and Austria. Baseline demographic and psychosocial characteristics were assessed by questionnaires. Indicators of disease severity (Heart Failure Survival Score, creatinine, cardiac index) and 12-month outcomes (death, high-urgency HTx, elective HTx, de-listing due to deterioration or improvement) were provided by Eurotransplant.



By 12 months, 33 patients died, 83 received an urgent HTx, 30 underwent an elective HTx, and 9 were de-listed due to clinical deterioration and 17 due to improvement. All measures of disease severity predicted outcomes. Controlling for disease severity, the number of social contacts contributed significantly to outcomes, favoring those who improved. Comparing socially isolated patients (<4 social contacts/month) who also had depression scores in the clinical range (high psychosocial risk group; n = 37) to those with >10 social contacts/month without depression (low psychosocial risk group; n = 47) revealed significant differences in the distribution of outcome frequencies (chi-square = 11.2, df = 4, p < 0.04). The high psychosocial risk group was more likely to have died/deteriorated and less likely to have improved than the low psychosocial risk group.



Regardless of disease severity, socially isolated HTx candidates who are also depressed may be at increased risk for clinical deterioration and mortality, indicating a need for psychosocial intervention.
Towards a Mixed-Reality Interface for Mind-Mapping

In this work, we have explored an approach based on the hybridisation of physical and digital content for mind-mapping activities at schools. Based on the literature in the fields of cognitive science and HCI, we have designed a mixed-reality (MR) interface called Reality-Map. We conducted a pilot study with 11 participants suggesting that learning and manipulating information about the brain and their cognitive functions could be improved by the use of such a MR interface compared to a traditional WIMP interface.
Analysis of cases of acute occlusive abdomen in elderly patients

Mechanisms of acute abdomen in the elderly patient are not different from the ones of young adults. What differs is the large number of associated diseases and specific geriatric pathology, ischemic disorders, diverticular disease. The diagnosis of acute abdomen in the elderly patient is difficult due to unclear symptoms, laboratory samples less modified and low cooperation. The article analyzed two groups of patients over 65 years, hospitalized in surgery in the last three years, with the diagnosis of acute surgical abdomen, from the point of view of the appearance of complications depending on the days of delay until surgery.
Chromosomal aberrations in lymphocytes predict human cancer: a report from the European Study Group on Cytogenetic Biomarkers and Health (ESCH).

Chromosomal aberrations (CAs), sister chromatid exchanges (SCEs), and micronuclei (MN) in peripheral blood lymphocytes have for decades been used as cytogenetic biomarkers to survey genotoxic risks in the work environment. The conceptual basis for this application has been the idea that increased cytogenetic damage reflects an enhanced cancer risk. Nordic and Italian cohorts have been established to evaluate this hypothesis, and analyses presented previously have shown a positive trend between CA frequency and increased cancer risk. We now report on a pooled analysis of updated data for 3541 subjects examined for CAs, 2703 for SCEs, and 1496 for MN. To standardize for interlaboratory variation, the results for the various cytogenetic end points were trichotomized on the basis of the absolute value distribution within each laboratory as "low" (1-33 percentile), "medium" (34-66 percentile), or "high" (67-100 percentile). In the Nordic cohort, there was an elevated standardized incidence ratio (SMR) for all cancer among subjects with high CA frequency [1.53; 95% confidence interval (CI), 1.13-2.05] but not for those with medium or low CA frequency. In the Italian cohort, a SMR in cancer of 2.01 (95% CI, 1.35-2.89) was obtained for those with a high CA frequency level, whereas the SMRs for those with medium or low did not noticeably differ from unity. Cox's proportional hazards models gave no evidence that the effect of CAs on total cancer incidence/mortality was modified by gender, age at test, or time since test. No association was seen between the SCEs or the MN frequencies and subsequent cancer incidence/mortality. The present study further supports our previous observation on the cancer predictivity of the CA biomarker, which seems to be independent of age at test, gender, and time since test. The risk patterns were similar within each national cohort. This result suggests that the frequency of CAs in peripheral blood lymphocytes is a relevant biomarker for cancer risk in humans, reflecting either early biological effects of genotoxic carcinogens or individual cancer susceptibility.