nils-herrmann/clean_scirepeval huggingface dataset:
Clinical evaluation of AZD1152, an i.v. inhibitor of Aurora B kinase, in patients with solid malignant tumors.

To determine, for each of two dosing schedules, the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of AZD1152, an Aurora B kinase inhibitor, and to evaluate its safety, biologic activity and pharmacokinetics (PK).



Patients with advanced solid malignancies were treated with escalating doses (100-650 mg) of AZD1152, administered as a 2-h infusion every 7 days (A) or 14 days (B). Adverse events (AEs), PK variables and tumor response were assessed.



Fifty-nine patients were treated; 19 in schedule A and 40 in schedule B. The MTDs were 200 and 450 mg, respectively. Neutropenia (with/without fever) was the most frequent AE and DLT in each schedule. Common Terminology Criteria of Adverse Events version 3.0 grade ≥3 neutropenia and leukopenia occurred in 58% and 11% of patients, respectively, in schedule A and 43% and 20%, respectively, in schedule B. No objective tumor responses were observed at any dose or schedule, although stable disease, as defined by RECIST, was achieved in 15 patients (25%) overall. Systemic exposure to AZD1152-hQPA (active drug) was observed by 1 h into the infusion and exhibited linear PK.



AZD1152 was generally well tolerated with neutropenia being the most frequently reported AE and DLT. Exposure to AZD1152-hQPA, the active drug of AZD1152, was linear.
Impact of prior chronic statin therapy and high-intensity statin therapy at discharge on circulating endothelial progenitor cell levels in patients with acute myocardial infarction: a prospective observational study

Endothelial progenitor stem cells (EPCs) are mobilized to the peripheral circulation in response to myocardial ischemia, playing a crucial role in vascular repair. Statins have been shown to stimulate EPCs. However, neither the impact of previous statin therapy on EPC response of acute myocardial infarction (AMI) patients nor the effect of post-AMI high-intensity statin therapy on the evolution of circulating EPC levels has yet been addressed. Therefore, we aimed to compare circulating EPC levels between patients receiving long-term statin therapy before the AMI and statin-naive patients and to assess the impact of high-intensity statin therapy at discharge on the evolution of circulating EPCs post-AMI. This is a prospective observational study of 100 AMI patients. Circulating EPCs (CD45dimCD34 + KDR + cells) and their subpopulation coexpressing the homing marker CXCR4 were quantified by the high-performance flow cytometer FACSCanto II in whole blood, in two different moments: within the first 24 h of admission and 3 months post-AMI. Patients were followed up clinically for 2 years. Patients previously treated with statins had significantly higher levels of EPCs coexpressing CXCR4 (1.9 ± 1.4 vs. 1.3 ± 1.0 cells/1,000,000 events, p = 0.031) than statin-naive patients. In addition, the subanalysis of diabetics (N = 38) also revealed that patients previously on statins had significantly greater numbers of both CD45dimCD34 + KDR + CXCR4+ cells (p = 0.024) and CD45dimCD34 + KDR + CD133+ cells (p = 0.022) than statin-naive patients. Regarding the evolution of EPC levels after the AMI, patients not on a high-intensity statin therapy at discharge had a significant reduction of CD45dimCD34 + KDR + and CD45dimCD34 + KDR + CXCR4+ cells from baseline to 3 months follow-up (p = 0.031 and p = 0.005, respectively). However, patients discharged on a high-intensity statin therapy maintained circulating levels of all EPC populations, presenting at 3 months of follow-up significantly higher EPC levels than patients not on an intensive statin therapy. Moreover, the high-intensity statin treatment group had significantly better clinical outcomes during the 2-year follow-up period than patients not discharged on a high-intensity statin therapy. Chronic statin therapy prior to an AMI strongly enhances the response of EPCs to myocardial ischemia, even in diabetic patients. Furthermore, high-intensity statin therapy after an AMI prevents the expected decrease of circulating EPC levels during follow-up. These results reinforce the importance of an early and intensive statin therapy in AMI patients.
Changes in arterial stiffness during continued infliximab treatment in patients with inflammatory arthropathies.

Chronic inflammatory arthropathies such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) are associated with an increased risk of cardiovascular disease. TNF-α antagonists may improve vascular function in these patients and thus be beneficial with regard to cardiovascular disease. This study evaluated arterial stiffness and disease activity between two infusions with a TNF-α antagonist (infliximab) in patients with inflammatory arthropathies on long-term infliximab therapy. Augmentation index (AIx), aortic pulse wave velocity (aPWV), and disease activity were measured in 17 patients with RA, AS, or PsA who had been treated with infliximab for at least 12 months. The patients were examined immediately before their infliximab infusion and thereafter every 10th day until their next infusion scheduled at week 4-8. AIx and aPWV did not change during the period between two infliximab infusions. The patients had a temporary improvement in the general disease activity assessed on visual analogue scales by the patients (P = 0.04) and the investigator (P = 0.02) after the infusion. In the group of patients with RA, the Disease Activity Score (DAS28) changed significantly in a similar manner (P = 0.003). C-reactive protein and erythrocyte sedimentation rate remained unchanged. Infliximab infusions did not alter aortic pulse wave velocity or augmentation index in patients with inflammatory arthropathies who were on long-term infliximab therapy. Reductions in the general disease activity and DAS28 were not reflected in alterations of aortic stiffness or augmentation index.
Plasma concentrations of beta-endorphin, adrenocorticotropic hormone, and cortisol in drinking and abstinent chronic alcoholics.

Previous studies of the relationship between the endogenous opioid system and alcohol consumption have reported contradictory results. To shed light on this connection, we compared plasma concentrations of beta-endorphin, adrenocorticotropic hormone, and cortisol in 70 alcoholic persons after different periods of abstinence and a group of 80 control subjects. Plasma beta-endorphin was decreased in alcoholics (18.61 +/- 1.38 vs. 39.31 +/- 3.44 pg/ml), even after more than 10 years' abstinence. This effect may mediated by the tetrahydroisoquinoline system, and may thus result from chronic alcohol consumption. On the other hand, lowered circulating concentrations of beta-endorphin may be a cause, rather than an effect, of alcoholism. Plasma levels of adrenocorticotropic hormone and cortisol did not differ in alcoholics and controls (19.29 +/- 1.66 vs. 13.27 +/- 1.85 pg/ml for ACTH, 20.37 +/- 0.78 vs. 17.22 +/- 0.64 ng/ml for cortisol), and thus appear to have no relation with chronic alcohol consumption.
Short-term evolution of spinal cord damage in multiple sclerosis: a diffusion tensor MRI study

The potential of diffusion tensor imaging (DTI) to detect spinal cord abnormalities in patients with multiple sclerosis has already been demonstrated. The objective of this study was to apply DTI techniques to multiple sclerosis patients with a recently diagnosed spinal cord lesion, in order to demonstrate a correlation between variations of DTI parameters and clinical outcome, and to try to identify DTI parameters predictive of outcome. A prospective single-centre study of patients with spinal cord relapse treated by intravenous steroid therapy was made. Patients were assessed clinically and by conventional MRI with DTI sequences at baseline and at 3 months. Sixteen patients were recruited. At 3 months, 12 patients were clinically improved. All but one patient had lower fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values than normal subjects in either inflammatory lesions or normal-appearing spinal cord. Patients who improved at 3 months presented a significant reduction in the radial diffusivity (p = 0.05) in lesions during the follow-up period. They also had a significant reduction in the mean ADC (p = 0.002), axial diffusivity (p = 0.02), radial diffusivity (p = 0.02) and a significant increase in FA values (p = 0.02) in normal-appearing spinal cord. Patients in whom the American Spinal Injury Association sensory score improved at 3 months showed a significantly higher FA (p = 0.009) and lower radial diffusivity (p = 0.04) in inflammatory lesion at baseline compared to patients with no improvement. DTI MRI detects more extensive abnormalities than conventional T2 MRI. A less marked decrease in FA value and more marked decreased in radial diffusivity inside the inflammatory lesion were associated with better outcome.
The Diagnostic Accuracy of Urine-Based Xpert MTB/RIF in HIV-Infected Hospitalized Patients Who Are Smear-Negative or Sputum Scarce

Hospitals in sub-Saharan Africa are inundated with HIV-infected patients and tuberculosis (TB) is the commonest opportunistic infection in this sub-group. Up to one third of TB-HIV co-infected patients fail to produce a sputum sample (sputum scarce) and diagnosis is thus often delayed or missed. We investigated the sensitivity of urine-based methods (Xpert MTB/RIF, LAM strip test and LAM ELISA) in such patients.



281 HIV-infected hospitalised patients with clinically suspected TB provided a spot urine sample. The reference standard was culture positivity for Mycobacterium tuberculosis on ≥1 sputum or extra-pulmonary sample. MTB/RIF was performed using 1 ml of both unprocessed and, when possible, concentrated urine. Each unconcentrated urine sample was also tested using the Clearview LAM ELISA and Alere LAM strip test. 42% (116/242) of patients had culture-proven TB. 18% (20/54) were sputum scarce. In sputum-scarce patients, the sensitivity of urine MTB/RIF and LAM ELISA was 40% (95%CI: 22-61) and 60% (95%CI: 39-78), respectively. Urine MTB/RIF specificity was 98% (95%CI: 95-100). Combined sensitivity of urine LAM ELISA and MTB/RIF was better than MTB/RIF alone [MTB/RIF and LAM: 70% (95%CI: 48-85) vs. MTB/RIF: 40% (95%CI: 22-61), p = 0.03]. Significant predictors of urine MTB/RIF positivity were CD4<50 cells/ml (p = 0.001), elevated protein-to-creatinine ratio (p<0.001) and LAM ELISA positivity (p<0.001). Urine centrifugation and pelleting significantly increased the sensitivity of MTB/RIF over unprocessed urine in paired samples [42% (95%CI: 26-58) vs. 8% (95%CI: 0-16), p<0.001]. Urine MTB/RIF-generated C(T) values correlated poorly with markers of bacillary burden (smear grade and time-to-positivity).



This preliminary study indicates that urine-based MTB/RIF, alone or in combination with LAM antigen detection, may potentially aid the diagnosis of TB in HIV-infected patients with advanced immunosuppression when sputum-based diagnosis is not possible. Concentration of urine prior to MTB/RIF-testing significantly improves sensitivity.
Genetic alterations of the cohesin complex genes in myeloid malignancies.

Somatic cohesin mutations have been reported in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). To account for the morphologic and cytogenetic diversity of these neoplasms, a well-annotated cohort of 1060 patients with myeloid malignancies including MDS (n = 386), myeloproliferative neoplasms (MPNs) (n = 55), MDS/MPNs (n = 169), and AML (n = 450) were analyzed for cohesin gene mutational status, gene expression, and therapeutic and survival outcomes. Somatic cohesin defects were detected in 12% of patients with myeloid malignancies, whereas low expression of these genes was present in an additional 15% of patients. Mutations of cohesin genes were mutually exclusive and mostly resulted in predicted loss of function. Patients with low cohesin gene expression showed similar expression signatures as those with somatic cohesin mutations. Cross-sectional deep-sequencing analysis for clonal hierarchy demonstrated STAG2, SMC3, and RAD21 mutations to be ancestral in 18%, 18%, and 47% of cases, respectively, and each expanded to clonal dominance concordant with disease transformation. Cohesin mutations were significantly associated with RUNX1, Ras-family oncogenes, and BCOR and ASXL1 mutations and were most prevalent in high-risk MDS and secondary AML. Cohesin defects were associated with poor overall survival (27.2 vs 40 months; P = .023), especially in STAG2 mutant MDS patients surviving >12 months (median survival 35 vs 50 months; P = .017).
Psychometric evaluation of the impact of cancer (IOC-CS) scale for young adult survivors of childhood cancer

Psychosocial outcomes derived from standardized and disease-specific measures are often used in pediatric oncology; however, the reliability, validity and utility of these instruments in adult survivors of childhood cancer have yet to be established. To develop and evaluate a new instrument that measures aspects of long-term survivorship not measured by existing tools. A new candidate instrument—the Impact of Cancer for childhood cancer survivors (IOC-CS)—was administered to childhood cancer survivors aged 18–39 who were 21 years of age or younger when diagnosed with cancer. Psychometric properties of newly derived scales were assessed. Factor analyses of items derived eight new and specific subscales: Life Challenges, Body/Health, Talking With Parents, Personal Growth, Thinking/Memory Problems, Health Literacy, Socializing and Financial Problems. Internal consistency measurements for these subscales ranged from 0.70 to 0.86. Expected associations within and among the IOC-CS subscales and standardized measures of health-related quality of life (HRQOL) were observed, as were some unexpected findings. Psychometric analyses indicated that this initial version of the IOC-CS measures distinct and relevant constructs for young adult survivors of childhood cancer. Future work is necessary to confirm the responsiveness and further validate the instrument in multiple and representative samples.
Urine lipoarabinomannan point-of-care testing in patients affected by pulmonary nontuberculous mycobacteria – experiences from the Danish Cystic Fibrosis cohort study

The urine lipoarabinomannan (LAM) strip test has been suggested as a new point-of-care test for active tuberculosis (TB) among human immunodeficiency virus (HIV) infected individuals. It has been questioned if infections with nontuberculous mycobacteria (NTM) affect assay specificity. We set forth to investigate if the test detects LAM in urine from a Danish cystic fibrosis (CF) population characterized by a high NTM prevalence and negligible TB exposure.



Patients followed at the Copenhagen CF Center were comprehensively screened for pulmonary NTM infection between May 2012 and December 2013. Urine samples were tested for LAM using the 2013 Determine™ TB LAM Ag strip test.



Three-hundred and six patients had a total of 3,322 respiratory samples cultured for NTM and 198 had urine collected (65%). A total of 23/198 (12%) had active pulmonary NTM infection. None had active TB. The TB-LAM test had an overall positive rate of 2.5% applying a grade 2 cut-point as positivity threshold, increasing to 10.6% (21/198) if a grade 1 cut-point was applied. Among patients with NTM infection 2/23 (8.7%) had a positive LAM test result at the grade 2 cut-point and 9/23 (39.1%) at the grade 1 cut -point. Test specificity for NTM diagnosis was 98.3% and 93.1 for grade 2 and 1 cut-point respectively.



This is the first study to assess urine LAM detection in patients with confirmed NTM infection. The study demonstrated low cross-reactivity due to NTM infection when using the recommended grade 2 cut-point as positivity threshold. This is reassuring in regards to interpretation of the LAM test for TB diagnosis in a TB prevalent setting. The test was not found suitable for NTM detection among patients with CF.
Validation of the Institut Curie simplified prognostic score for breast cancer meningeal carcinomatosis.

Breast cancer is the leading nonhematologic cause of meningeal carcinomatosis (MC), a unusual metastatic site. Its treatment generally relies on intrathecally and/or systematically delivered chemotherapy, combined with radiotherapy or surgery when needed. However, the overall survival (OS) of patients with proven MC is short, generally no longer than 6 months after the diagnosis of MC . A retrospective study on 91 breast cancer MC diagnosed and treated homogeneously by a high-dose intrathecal methotrexate regimen [2] at the Institut Curie (Paris, France) from 2000 to 2007 has been recently reported . This study retrieved four adverse independent prognostic factors at MC diagnosis: performance status (PS) of three to four, elevated Cyfra 21-1 marker in the cerebrospinal fluid (CSF), negative hormone receptors (HR) status and more than three previous chemotherapy lines for metastatic disease. Two prognostic scores were derived from these results, based on the number of adverse prognostic factors: the complete score included the four prognostic factors, whereas the simplified score did not include CSF Cyfra 21-1 as its dosage is not made routinely in this setting. Both prognostic scores allowed to classify patients into three groups with poor, intermediate and good prognosis (median OS of 2, 4 and 12 months, respectively). These scores required further validation. A retrospective validation of the simplified prognostic score has been conducted in patients diagnosed with breast cancer MC at the Institut Jules Bordet (Brussels, Belgium), after approval of the local ethic committee. Briefly, the electronic file of each of the 926 patients who underwent CSF cytological analysis from 01/2000 to 07/2010 were screened manually for MC diagnosis (tumor cells in CSF): 88 patients had both breast letters to the editor Annals of Oncology
Comparison of the university hospital and county hospitals in western Sweden to identify potential weak links in the early chain of care for acute stroke: results of an observational study

To identify weak links in the early chain of care for acute stroke.



9 emergency hospitals in western Sweden, each with a stroke unit, and the emergency medical services (EMS).



All patients hospitalised with a first and a final diagnosis of stroke-between 15 December 2010 and 15 April 2011. The university hospital in the city of Gothenburg was compared with 6 county hospitals.  (1) The system delay, that is, median delay time from call to the EMS until diagnosis was designated as the primary end point. Secondary end points were: (2) the system delay time from call to the EMS until arrival in a hospital ward, (3) the use of the EMS, (4) priority at the dispatch centre and (5) suspicion of stroke by the EMS nurse.



In all, 1376 acute patients with stroke (median age 79 years; 49% women) were included. The median system delay from call to the EMS until (1) diagnosis (CT scan) and (2) arrival in a hospital ward was 3 h and 52 min and 4 h and 22 min, respectively. The system delay (1) was significantly shorter in county hospitals. (3) The study showed that 76% used the EMS (Gothenburg 71%; the county 79%; p<0.0001). (4) Priority 1 was given at the dispatch centre in 54% of cases. (5) Stroke was suspected in 65% of cases. A prenotification was sent in 32% (Gothenburg 52%; the county 20%; p<0.0001).



System delay is still long and only a small fraction of patients received thrombolysis. Three of four used the EMS (more frequent in the county). They were given the highest priority at the dispatch centre in half of the cases. Stroke was suspected in two-thirds of the cases, but a prenotification was seldom sent to the hospital.
Twelve-month consumption of a polyphenol extract from olive (Olea europaea) in a double blind, randomized trial increases serum total osteocalcin levels and improves serum lipid profiles in postmenopausal women with osteopenia.

Osteoporosis is a skeletal disorder characterized by impaired bone turnover and compromised bone strength, thereby predisposing to increased risk of fracture. Preclinical research has shown that compounds produced by the olive tree (Olea europaea), may protect from bone loss, by increasing osteoblast activity at the expense of adipocyte formation. The aim of this exploratory study was to obtain a first insight on the effect of intake of an olive extract on bone turnover in postmenopausal women with decreased bone mass (osteopenia).



For that, a double blind, placebo-controlled study was performed in which participants were randomly allocated to either treatment or placebo groups.



64 osteopenic patients, with a mean bone mineral density (BMD) T-score between -1.5 and -2.5 in the lumbar spine (L2-L4) were included in the study.



PARTICIPANTS received for 12 months daily either 250 mg/day of olive extract and 1000 mg Ca (treatment) or 1000 mg Ca alone (placebo). Primary endpoints consisted of evaluation of bone turnover markers. Secondary endpoints included BMD measurements and blood lipid profiles.



After 12 months, the levels of the pro-osteoblastic marker osteocalcin were found to significantly increase in the treatment group as compared to placebo. Simultaneously, BMD decreased in the placebo group, while remaining stable in the treatment group. In addition, improved lipid profiles were observed, with significant decrease in total- and LDL-cholesterol in the treatment group.



This exploratory study supports preclinical observations and warrants further research by showing that a specific olive polyphenol extract (Bonolive®) affects serum osteocalcin levels and may stabilize lumbar spine BMD. Moreover, the improved blood lipid profiles suggest additional health benefits associated to the intake of the olive polyphenol extract.
A randomized controlled trial of simulation-based teaching versus traditional instruction in medicine: a pilot study among clinical medical students.

To compare simulator-based teaching with traditional instruction among clinical medical students.



Randomized controlled trial with written pre-post testing. Third-year medical students (n = 38) received either a myocardial infarction (MI) simulation followed by a reactive airways disease (RAD) lecture, or a RAD simulation followed by an MI lecture.



Mean pre-post test score improvement was seen across teaching modalities (overall change score [simulation] = 8.8 [95% CI = 2.3-15.3], pretest [62.7]; change score [lecture] = 11.3 [95% CI = 5.7-16.9], pretest [59.7]). However, no significant differences were observed between simulator-based teaching and lecture, in either subject domain.



After a single instructional session for clinical medical students, differences between simulator-based teaching and lecture could not be established by the written test protocols used in this pilot. Future studies should consider the effects of iterative exposure assessed by clinical performance measures across multiple centers.