nils-herrmann/clean_scirepeval huggingface dataset:
A feasibility study of weekly docetaxel with capecitabine in ovarian cancer: a promising combination of two active drugs with a potential for synergism.

To evaluate the safety and efficacy of weekly docetaxel with capecitabine in patients with recurrent/persistent epithelial ovarian cancer (EOC).



Women treated for recurrent/persistent EOC in our department (January 2004 through December 2005) were recruited into this feasibility study. They received 35 mg/m(2) docetaxel on days 1 and 8 and 1,000 mg/m(2) capecitabine twice daily on days 1-14 in a 21-day cycle.



Nine patients were enrolled. The median age was 64 years (37-80). Time to progression ranged from 1.67 to 11.27 months: 1 had complete response, 3 had partial responses, 4 had stable disease and 1 had disease progression. There was no grade 3 or 4 bone marrow toxicity. Nonhematological toxicity included partial hair loss (n = 4), fatigue (n = 7), hand and foot syndrome (n = 2), diarrhea (n = 5) and fluid retention syndrome (n = 1).



There was good antitumor activity but frequent moderate-to-severe nonhematological toxicities when weekly docetaxel and capecitabine were used as second-line therapy for recurrent EOC. Further investigation of this combination is warranted.
VE1 immunohistochemistry predicts BRAF V600E mutation status and clinical outcome in colorectal cancer.

VE1 is a monoclonal antibody detecting mutant BRAFV(600E) protein by immunohistochemistry. Here we aim to determine the inter-observer agreement and concordance of VE1 with mutational status, investigate heterogeneity in colorectal cancers and metastases and determine the prognostic effect of VE1 in colorectal cancer patients.



Concordance of VE1 with mutational status and inter-observer agreement were tested on a pilot cohort of colorectal cancers (n = 34), melanomas (n = 23) and thyroid cancers (n = 8). Two prognostic cohorts were evaluated (n = 259, Cohort 1 and n = 226, Cohort 2) by multiple-punch tissue microarrays. VE1 staining on preoperative biopsies (n = 118 patients) was compared to expression in resections. Primary tumors and metastases from 13 patients were tested for VE1 heterogeneity using a tissue microarray generated from all available blocks (n = 100 blocks).



Inter-observer agreement was 100% (kappa = 1.0). Concordance between VE1 and V600E mutation was 98.5%.  VE1 positivity (seen in 13.5%) was associated with older age (p = 0.0175) and MLH1 deficiency (p < 0.0001). Cohort 2: VE1 positivity (seen in 12.8%) was associated with female gender (p = 0.0016), right-sided tumor location (p < 0.0001), higher tumor grade (p < 0.0001) and mismatch repair (MMR)-deficiency (p < 0.0001). In survival analysis, MMR status and postoperative therapy were identified as possible confounding factors. Adjusting for these features, VE1 was an unfavorable prognostic factor. Preoperative biopsy staining matched resections in all cases except one. No heterogeneity was found across any primary/metastatic tumor blocks.



VE1 is highly concordant for V600E and homogeneously expressed suggesting staining can be analysed on resection specimens, preoperative biopsies, metastatic lesions and tissue microarrays.
Effect of smoking cessation and relapse on cardiovascular levels and reactivity

This study was designed to investigate the effect of smoking cessation on heart rate, blood pressure, and finger temperature absolute levels and reactivity to a range of laboratory challenges. The 148 quitters (mean age=43.3 years, mean amount smoked=24.9 cigarettes per day, mean years smoked=25.2) completed three assessments: an average of 4±2.8 days before cessation (Exam 1), an average of 2±1.0 days after cessation (Exam 2), and an average of 20±5.5 days after cessation (Exam 3). A nonsmoking group (n=39) was similarly assessed three times to control for effects related to repeated testing. Comparison of group changes from Exam 1 to Exam 2 indicated that smoking cessation produced a significant decrease in heart rate during rest and during all stressors (mean=−8.9 bpm). Those quitters who remained abstinent or smoked occasionally showed minimal changes in heart rate from Exam 2 to Exam 3, but those quitters who returned to their previous smoking level showed a significant increase in heart rate from Exam 2 to Exam 3. None of the indices of cardiovascular reactivity changed across exams, and neither did absolute levels of blood pressure or finger temperature at rest or during stressors. The possible mechanisms producing a selective heart rate decline after smoking cessation in the absence of pressor or vasodilation effects are discussed.
Non invasive contact electrodes for in vivo localized cutaneous electropulsation and associated drug and nucleic acid delivery.

For an effective tissue controlled electropermeabilization as requested for electrochemotherapy and electrogenotherapy, it is very important to have informations about the electric field distribution provided by a defined set of electrodes. Computer simulations using the finite element models approach predicted the associated field distributions and currents. Phantoms made of gels with well-defined electrical conductance were used to measure the current responses of a new electrode geometry (wires), A good agreement between the measured and predicted currents was observed supporting the validity of the prediction for the field distribution. Field distribution was observed to be very localized and highly homogeneous with the new concept of contact wire electrodes. They allowed to focus the field effect along the surface of the tissue to induce a controlled release of drugs or plasmids. Non invasive (contact) electrodes can be moved rapidly on the body and avoid puncturing the skin and the tissue. They can be used for large surface effects, to treat the skin and subcutaneous tumors. The use of contact electrodes after drug or DNA intradermal injection were validated by clinical treatment of large surface skin tumors and by in vivo imaging of permeabilization or of gene expression.
Symptoms of specific and generalized social phobia: an examination of discriminant validity and structural relations with mood and anxiety symptoms.

Current models divide social phobia into specific (SSP) and generalized (GSP) subtypes and suggest strong overlap between GSP and avoidant personality disorder (APD). Meanwhile, other research suggests reclassifying anxiety and mood disorders as fear and distress disorders. To unify these separate lines of research, this study was designed to test the hypothesis that SSP is more related to fear disorders (e.g., panic and phobias), whereas GSP and APD are more related to distress disorders (e.g., depression and generalized anxiety). Confirmatory factor analysis suggested the best-fitting model had symptoms of GSP, APD, and depression loading on one factor, and symptoms of SSP, panic, and specific phobias loading on a second factor. Key components of this model were (a) the inclusion of GAD symptoms reduced model fit and (b) GSP and APD symptoms significantly predicted SSP symptoms; this is consistent with conceptualizations of individuals with both GSP and SSP reporting performance anxiety.
Sleep-related eating disorder and zolpidem: an open interventional cohort study.

Sleep-related eating disorder (SRED) is a newly recognized parasomnia that describes a clinical condition of compulsive eating under an altered level of consciousness during sleep. The prevalence rate varies from 4% to 16.7% among different clinical psychiatric populations.1,2 The exact etiology of SRED is unclear, but it is postulated that SRED might share features of both sleepwalking and eating disorders.3 In addition, there have been accumulating reports of SRED related to the use of various psychotropic medications including triazolam, zolpidem, olanzapine, risperidone, and combinations of psychotropics.4–8 Among these drugs, recent attention has focused on zolpidem, a nonbenzodiazepine hypnotic. Our clinical epidemiologic study in psychiatric outpatients2 showed that 1 out of 7 subjects regularly taking zolpidem could develop SRED in their lifetime. In addition, among a psychiatric population, most of the adult-onset sleepwalking cases were highly comorbid with SRED  Thus, there seems to be a robust association of zolpidem and SRED on the basis of both cross-sectional clinical series and epidemiologic evidence. Warnings were issued in 2007 by both the Therapeutic Goods Administration of Australia10 and US Food and Drug Administration11 with regard to SRED as a potential side effect of zolpidem. Nonetheless, in order to confirm a definite association of zolpidem and SRED, resolution or reduction of SRED symptoms upon cessation of zolpidem treatment should be demonstrated. In particular, the episodic nature of the SRED attacks would argue the need for a longer-term follow-up period to document a clear resolution of the symptoms.
High-dose intravenous immunoglobulin treatment in cryptogenic West and Lennox-Gastaut syndrome; an add-on study

In an add-on pilot study, a group of 15 children with cryptogenic and intractable West syndrome (3) and Lennox-Gastaut syndrome (12) received intravenous immunoglobulin (IVIg, 0.4g/kg body weight per day for 5 consecutive days, followed by the same dose once every 2 weeks for 3 months). Five patients had been treated previously with ACTH without success. The reduction in clinical seizures averaged 70%. Electroencephalographic (EEG) recordings revealed a mean reduction in epileptic discharges of 40%. In all 15 patients, acceleration of EEG background activity occurred, and psychomotor development improved. Prior to IVIg administration, CSF examinations were normal. After IVIg administration, the serum total IgG concentration increased by an average of 76%, and the CSF IgG concentration by 44%. According to our data, IVIg crosses the blood-CSF barrier, and might be effective in the treatment of West syndrome and Lennox-Gastaut syndrome. We suggest it should be considered when other treatments, such as ACTH, have failed.
Exaggerated exercise pressor reflex in adults with moderately elevated systolic blood pressure: role of purinergic receptors.

The neurocirculatory responses to exercise are exaggerated in hypertension, increasing cardiovascular risk, yet the mechanisms remain incompletely understood. The aim of this study was to examine the in vitro effectiveness of pyridoxal-5-phosphate as a purinergic (P2) receptor antagonist in isolated murine dorsal root ganglia (DRG) neurons and the in vivo contribution of P2 receptors to the neurocirculatory responses to exercise in older adults with moderately elevated systolic blood pressure (BP). In vitro, pyridoxal-5-phosphate attenuated the ATP-induced increases in [Ca(2+)](i) (73 ± 15 vs. 11 ± 3 nM; P < 0.05). In vivo, muscle sympathetic nerve activity (MSNA; peroneal microneurography) and arterial BP (Finometer) were assessed during exercise pressor reflex activation (static handgrip followed by postexercise ischemia; PEI) during a control trial (normal saline) and localized P2 receptor blockade (pyridoxal-5-phosphate). Compared with normotensive adults (63 ± 2 yr, 117 ± 2/70 ± 2 mmHg), adults with moderately elevated systolic BP (65 ± 1 yr, 138 ± 5/79 ± 3 mmHg) demonstrated greater increases in MSNA and BP during handgrip and PEI. Compared with the control trial, local antagonism of P2 receptors during PEI partially attenuated MSNA (39 ± 4 vs. 34 ± 5 bursts/min; P < 0.05) in adults with moderately elevated systolic BP. In conclusion, these data demonstrate pyridoxal-5-phosphate is an effective P2 receptor antagonist in isolated DRG neurons, which are of particular relevance to the exercise pressor reflex. Furthermore, these findings indicate that exercise pressor reflex function is exaggerated in older adults with moderately elevated systolic BP and further suggest a modest role of purinergic receptors in evoking the abnormally large reflex-mediated increases in sympathetic activity during exercise in this clinical population.
Evaluation of magnetic resonance imaging and clinical outcome after tissue-engineered cartilage implantation: prospective 6-year follow-up study

Autologous chondrocyte implantation (ACI) is an important procedure when repairing cartilage defects of the knee. We previously reported several basic studies on tissue-engineered cartilage, and conducted a multicenter clinical study in 2009. In this clinical study, we evaluated the patients' clinical scores and MRI findings before and after tissue-engineered cartilage implantation, and compared the data obtained at 1 year and approximately 6 years post-implantation.



Fourteen patients who underwent implantation of tissue-engineered cartilage to repair cartilage defects of the knee were evaluated. Tissue-engineered cartilage was produced by culturing autologous chondrocytes three dimensionally in atelocollagen gel. The patients were evaluated clinically using the Lysholm score, and the original knee-function score at pre-implantation and at 1 year and approximately 6 years post-implantation. MRI scans were obtained at the same observation periods. A modified magnetic resonance observation of cartilage repair tissue (MOCART) system was used to quantify clinical efficacy based on the MRI findings.



In approximately 6 years of follow-up, none of the 14 patients reported any subjective symptoms of concern. The mean Lysholm score and the original knee-function score (63.0 ± 10.1, 59.9 ± 5.7) significantly improved at 1 year after implantation (86.4 ± 11.8, 94.1 ± 9.2), and were maintained until 6 years after implantation (89.8 ± 6.2, 89.9 ± 11.2), although some patients showed deterioration of Lysholm and original knee scores between 1 year post-implantation and the final follow-up. The mean MOCART score was 13.2 ± 12.0 pre-implantation, and 62.5 ± 24.7 at 1 year and 70.7 ± 22.7 at approximately 6 years post-implantation. The MOCART scores at 1 year and 6 years were significantly higher than the pre-implantation score, but there was no significant difference between the scores at 1 and 6 years, indicating that the MRI results at 1 year after implantation were maintained for the next 5 years.



The clinical scores and MRI findings after implantation of tissue-engineered cartilage were improved at 1 year after implantation and were maintained until 6 years after implantation.
ASXL1 mutations in younger adult patients with acute myeloid leukemia: a study by the German-Austrian Acute Myeloid Leukemia Study Group.

We studied 1696 patients (18 to 61 years) with acute myeloid leukemia for ASXL1 mutations and identified these mutations in 103 (6.1%) patients. ASXL1 mutations were associated with older age (P<0.0001), male sex (P=0.041), secondary acute myeloid leukemia (P<0.0001), and lower values for bone marrow (P<0.0001) and circulating (P<0.0001) blasts. ASXL1 mutations occurred in all cytogenetic risk-groups; normal karyotype (40%), other intermediate-risk cytogenetics (26%), high-risk (24%) and low-risk (10%) cytogenetics. ASXL1 mutations were associated with RUNX1 (P<0.0001) and IDH2(R140) mutations (P=0.007), whereas there was an inverse correlation with NPM1 (P<0.0001), FLT3-ITD (P=0.0002), and DNMT3A (P=0.02) mutations. Patients with ASXL1 mutations had a lower complete remission rate (56% versus 74%; P=0.0002), and both inferior event-free survival (at 5 years: 15.9% versus 29.0%; P=0.02) and overall survival (at 5 years: 30.3% versus 45.7%; P=0.0004) compared to patients with wildtype ASXL1. In multivariable analyses, ASXL1 and RUNX1 mutation as a single variable did not have a significant impact on prognosis. However, we observed a significant interaction (P=0.04) for these mutations, in that patients with the genotype ASXL1(mutated)/RUNX1(mutated) had a higher risk of death (hazard ratio 1.8) compared to patients without this genotype. ASXL1 mutation, particularly in the context of a coexisting RUNX1 mutation, constitutes a strong adverse prognostic factor in acute myeloid leukemia.
Postal and face-to-face administration of stroke outcome measures: can mixed modes be used?

Different modes of administration are used to collect stroke outcomes, even within the same study, potentially leading to different results. We investigated the effect of administration mode (postal questionnaire; face-to-face interview) on self-reports of activities of daily living and mood.



The study was nested within a poststroke motivational interviewing trial. Activities of daily living (Barthel; Nottingham Extended) and mood (General Health Questionnaire; Yale) were collected at 3 and 12 months via postal questionnaire. Participants were approached to respond again via face-to-face interview. Paired t tests (McNemar test) and intraclass correlation coefficients (Cohen κ) were used, with 95% CI, to compare scores (items).



Forty-four participants consented. Only Barthel scores were significantly different; they were 1.0 (95% CI, 0.5-1.6) higher face-to-face. The intraclass correlation coefficient for the Barthel was 0.90; for the other scales it was between 0.83 and 0.87. The Yale κ was 0.72.



Modes of administration might be used interchangeably, albeit in conjunction with corrections for the Barthel.
Cohort Profile: Swedish Twin Study on Prediction and Prevention of Asthma (STOPPA).

Asthma is a common childhood disease and several risk factors have been identified; however, the impact of genes and environment is not fully understood. The aim of the Swedish Twin study On Prediction and Prevention of Asthma (STOPPA) is to identify environmental (birth characteristics and early life) and genetic (including epigenetic) factors as determinants for asthmatic disease. Based on the Child and Adolescent Twin Study in Sweden (CATSS) (parental interview at 9 or 12 years, N ~23,900) and an asthma and/or wheezing algorithm, we identified a sample of monozygotic (MZ) and dizygotic (DZ) same-sexed twin pairs. The twin pairs were classified as asthma concordant (ACC), asthma discordant (ADC) and healthy concordant (HCC). A sample of 9- to 14-year-old twins and their parents were invited to participate in a clinical examination. Background characteristics were collected in questionnaires and obtained from the National Health Registers. A clinical examination was performed to test lung function and capacity (spirometry with reversibility test and exhaled nitric oxide) and collect blood (serology and DNA), urine (metabolites), feces (microbiota), and saliva (cortisol). In total, 376 twin pairs (752 individual twins) completed the study, response rate 52%. All participating twins answered the questionnaire and >90% participated in lung function testing, blood-, and saliva sampling. This article describes the design, recruitment, data collection, measures, and background characteristics, as well as ongoing and planned analyses in STOPPA. Potential gains of the study include the identification of biomarkers, the emergence of candidates for drug development, and new leads for prevention of asthma and allergic disease.
Severe vitamin D deficiency among heart and liver transplant recipients.

Although patients with end-stage organ failure are at high risk for vitamin D deficiency because of limited sunlight exposure and hepatic dysfunction, few studies have measured 25-hydroxy vitamin D (25OHD) at the time of transplantation.



We measured serum 25OHD immediately after transplantation in 69 heart and liver transplant recipients.



Forty-six heart and 23 liver transplant recipients were evaluated (mean age 53 yr). Mean 25OHD was well below the lower limit of the normal range (43.2 +/- 21.2 nmol/L). Ninety-one percent had levels below 75 nmol/L, the threshold commonly used to denote sufficiency, and 71% had levels below 50 nmol/L. Severe deficiency (25OHD <25 nmol/L) was found in 16%. Vitamin D levels did not differ by race, age, gender, or season. Mean 25OHD was lower among liver than heart transplant recipients (34.4 +/- 17.5 vs. 47.7 +/- 20.7 nmol/L; p < 0.03). Among liver transplant recipients, 22% had undetectable levels (<17 nmol/L).



Vitamin D deficiency is highly prevalent among heart and liver transplant recipients; those with liver failure are at greatest risk. As vitamin D deficiency has many serious skeletal and extra-skeletal sequelae, physicians who treat transplant patients should maintain a high degree of vigilance for this problem.
Intragastric acidity as a predictor of the success of Helicobacter pylori eradication: a study in peptic ulcer patients with omeprazole and amoxicillin.

Omeprazole plus amoxicillin cures Helicobacter pylori infection. The hypothesis was tested that low acidity is a predictor of outcome. Fifty patients with relapsing or complicated, or both H pylori positive duodenal (n = 25) or gastric ulcer (n = 25) were randomly treated with either omeprazole 20 mg twice daily plus amoxicillin 1 g twice daily or with omeprazole 40 mg twice daily plus amoxicillin 1 g twice daily over two weeks. After one week of combined treatment, a 24 hour gastric pH measurement was performed in all patients. H pylori cure rate was 67%. Patients who later turned out to be cured had higher pH values during night time and after meals (p < 0.05). In an explorative analysis drug compliance, smoking, location of the ulcer (duodenum versus stomach), age, and grade of body gastritis were additional predictors of the outcome. Smoking (p = 0.006), compliance (p = 0.037), duodenal ulcer disease (p = 0.065), and young age (p = 0.021) were related to high acidity. In conclusion, the success of eradication treatment with omeprazole and amoxicillin in ulcer patients infected with H pylori depends on intragastric pH. Drug compliance, smoking habits, location of ulcer, age, and activity of body gastritis are other predictors and in part related to intragastric acidity.
Tolerability assessment of maximal androgen blockade with 50 mg daily of bicalutamide and castration in patients with advanced prostate cancer.

Androgen is the most important growth factor for the development and growth of prostatic adenocarcinomas. For patients with advanced prostate cancer, hormonal manipulation including castration and antiandrogen therapy is a well-established mode of treatment. The choice of hormonal therapy for prostate cancer depends not only on the desired progression-free and overall survival, but also on the patient's quality of life, treatment costs, and treatment toxicities.



 in combination with castration; we also investigated whether the prostate-specific antigen (PSA) rates of change at weeks 4 and 12 were indicative of an increased risk of progression.



Thirty-seven patients were enrolled in the study from December 1996 to June 1999 in Chang Gung Memorial Hospital, Taoyuan. The overall incidence rate of adverse events was 27%. The most frequent adverse event was hot flushes (5.4%). The rate of overall disease response was 85.3%. No evidence was found for any predictive relationship between serum PSA concentration and risk of progression.



The overall results indicate that bicalutamide administered as a 50-mg daily dosage in combination with castration is a well-tolerated therapy for the treatment of patients with advanced prostate cancer.