nils-herrmann/clean_scirepeval huggingface dataset:
A phase II study of sequential 5-fluorouracil, epirubicin and cyclophosphamide (FEC) and paclitaxel in advanced breast cancer (Protocol PV BC 97/01)

Sequential administration of the association of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) and paclitaxel could be better tolerated than the association of an anthracycline and paclitaxel while having a similar antitumour effect. 69 patients with advanced breast cancer previously untreated with anthracyclines or paclitaxel entered a phase II multicentre study in which FEC was followed by paclitaxel. Both regimens were administered 4 times every 21 days. The median follow-up is 20 months and 38/69 patients have died. Grade III–IV toxicity was acceptable. Leukopenia occurred in 26% of patients, thrombocytopenia in 2% and anaemia in 4%. One patient had reversible heart failure during FEC therapy. Peripheral neuropathy and arthralgia-myalgia occurred in 9% and 4% of patients, respectively and one patient had respiratory hypersensitivity during paclitaxel treatment. 9 patients did not complete therapy because of: treatment refusal (n= 1), cardiac toxicity (n= 1), early death during FEC chemotherapy (n= 1), major protocol violations (n= 4), hypersensitivity reaction (n= 1) and early death during paclitaxel chemotherapy (n= 1). The overall response rate was 65% (95% CI = 53–76), and 7% of patients had stable disease. Therapy was defined as having failed in 28% of patients because they were not evaluable (13%) or had progressive disease (15%). The median time to progression and survival are 13.2 and 23.5 months, respectively. Sequential FEC-paclitaxel is a suitable strategy for patients with metastatic breast cancer who have not been previously treated with anthracyclines and/or taxanes. In fact, it avoids major haematologic toxicity and has a good antitumour effect.
Atorvastatin in dyslipidaemia of the nephrotic syndrome.

The combined dyslipidaemia that accompanies the nephrotic syndrome increases the cardiovascular risk and appears to worsen long-term renal function. Our aim was to determine the efficacy and safety of 10 mg atorvastatin in the control of dyslipidaemia in these patients. We carried out a prospective, open, 6 month study of 10 patients with primary or secondary nephrotic syndrome (proteinuria >3.5 g/day, hypoalbuminaemia, oedema and hyperlipidaemia). The changes in lipids and plasma lipoproteins were measured, as well as the safety profile (transaminases, creatine phosphokinase, fibrinogen and antithrombin III activity) and parameters of renal function. The addition of 10 mg atorvastatin daily for 6 months resulted in a 41% reduction in low density lipoprotein (LDL) cholesterol and 31% in triglycerides (both P < 0.05), and a 15% increase in high density lipoprotein (HDL) cholesterol (NS). The drug was well tolerated and there was no change in the safety profile or deterioration in renal function. In fact, the levels of proteinuria fell in all but one patient (6.2 +/- 2.6 vs 4.8 +/- 2.5 g/24 h; P < 0.05). Atorvastatin, at the above dose, and for the time used proved to be a safe drug that effectively reduced dyslipidaemia in patients with nephrotic syndrome.
Impact of an Educational Program to Reduce Healthcare Resources in Community-Acquired Pneumonia: The EDUCAP Randomized Controlled Trial

Additional healthcare visits and rehospitalizations after discharge are frequent among patients with community-acquired pneumonia (CAP) and have a major impact on healthcare costs. We aimed to determine whether the implementation of an individualized educational program for hospitalized patients with CAP would decrease subsequent healthcare visits and readmissions within 30 days of hospital discharge.



A multicenter, randomized trial was conducted from January 1, 2011 to October 31, 2014 at three hospitals in Spain. We randomly allocated immunocompetent adults patients hospitalized for CAP to receive either an individualized educational program or conventional information before discharge. The educational program included recommendations regarding fluid intake, adherence to drug therapy and preventive vaccines, knowledge and management of the disease, progressive adaptive physical activity, and counseling for alcohol and smoking cessation. The primary trial endpoint was a composite of the frequency of additional healthcare visits and rehospitalizations within 30 days of hospital discharge. Intention-to-treat analysis was performed.



We assigned 102 patients to receive the individualized educational program and 105 to receive conventional information. The frequency of the composite primary end point was 23.5% following the individualized program and 42.9% following the conventional information (difference, -19.4%; 95% confidence interval, -6.5% to -31.2%; P = 0.003).



The implementation of an individualized educational program for hospitalized patients with CAP was effective in reducing subsequent healthcare visits and rehospitalizations within 30 days of discharge. Such a strategy may help optimize available healthcare resources and identify post-acute care needs in patients with CAP.
The Role of Mammographic Calcification in the Neoadjuvant Therapy of Breast Cancer Imaging Evaluation

Investigate the patterns of mammographically detected calcifications before and after neoadjuvant chemotherapy (NACT) to determine their value for efficacy evaluation and surgical decision making.



187 patients with malignant mammographic calcifications were followed to record the appearances and changes in the calcifications and to analyze their responses to NACT.



Patients with calcifications had higher rates of hormonal receptor (HR) positive tumors (74.3% versus 64.6%) and HER2 positive tumors (51.3% versus 33.4%, p = 0.004) and a similar pathologic complete response (pCR) rate compared to patients without calcifications (35.4% versus 29.8%). After NACT, the range of calcification decreased in 40% of patients, increased in 7.5% and remained stable in 52.5%; the calcification density decreased in 15% of patients, increased in 7.5% and remained stable in 77.5%; none of these change patterns were related to tumor response rate. No significant correlation was observed between the calcification appearance (morphology, distribution, range, diameter or density) and tumor subtypes or pCR rates. Among patients with malignant calcifications, 54 showed calcifications alone, 40 occurred with an architectural distortion (AD) and 93 with a mass. Calcifications were observed inside the tumor in 44% of patients and outside in 56%, with similar pCR rates and patterns of change.



Calcification appearance did not clearly change after NACT, and calcification patterns were not related to pCR rate, suggesting that mammogram may not accurate to evaluate tumor response changes. Microcalcifications visible after NACT is essential for determining the extent of excision, patients with calcifications that occurred outside of the mass still had the opportunity for breast conservation.
Transsphenoidal hypophysectomy for four dogs with pituitary ACTH-producing adenoma.

Four dogs diagnosed as pituitary-dependent hyperadrenocorticism were treated with transsphenoidal hypophysectomy and postoperative hormone supplementation therapy. On histological examination of the resected tissues, the tumors were ACTH-producing adenoma of the anterior lobe. Clinical signs such as alopecia and calcinosis cutis, as well as endocrinological abnormalities, were markedly alleviated after surgery. The clinical courses of these 4 dogs suggest that transsphenoidal hypophysectomy may be a useful treatment for pituitary-dependent hyperadrenocorticism.
Antihypertensive effect of Valyl-Tyrosine, a short chain peptide derived from sardine muscle hydrolyzate, on mild hypertensive subjects

The present study was conducted to determine whether Valyl-Tyrosine (VY) has an antihypertensive effect on high-normal blood pressure and mild essential hypertension, as well as spontaneous hypertensive rats (SHR). A randomised double-blind placebo-controlled study was carried out on 29 volunteers. A 100-ml drink containing 3 mg of VY and a 100-ml placebo drink were prepared. The subjects were grouped as VY(16M/1F, 45.5 ± 3.2 years, 146.4 ± 2.3/90.5 ± 1.8 mm Hg) and the placebo (P) (11 M/1F, 48.8 ± 3.0 years, 145.5 ± 2.4/92.3 ± 1.8 mm Hg). At 3 weeks of the control (C) period, a VY- or P-drink was administered twice a day for 4 weeks in the experimental (E) period and during the 4-week recovery period, neither drink was given to either group. Blood pressure (BP) was measured every week in the morning in the sitting position. Blood specimens were taken on the last day of the C and E periods. In the VY-group, reduction in systolic (S) and diastolic (D) BP was 9.7 and 5.3 mm Hg (P < 0.001) at 1 week, and 9.3 and 5.2 mm hg (P < 0.001) at 4 weeks, following the start of the e period, respectively. neither sbp nor dbp changed in the p-group. bp in the vy-group increased gradually by the end of the recovery period. plasma angiotensin (ang) i and vy concentrations significantly increased while ang ii and aldosterone significantly decreased after vy administration in the vy-group. vy appeared to have a significant antihypertensive effect on mild hypertensive subjects via ang i-converting enzyme inhibition, as well as shr, but no adverse effects could be detected at all.
Association of the response to tumor necrosis factor antagonists with plasma type I interferon activity and interferon-beta/alpha ratios in rheumatoid arthritis patients: a post hoc analysis of a predominantly Hispanic cohort.

Despite the substantial clinical efficacy of tumor necrosis factor alpha (TNFalpha) antagonist therapy in patients with rheumatoid arthritis (RA), some patients respond poorly to such agents. Since an interferon (IFN) signature is variably expressed among RA patients, we investigated whether plasma type I IFN activity might predict the response to TNF antagonist therapy.



RA patients (n = 35), the majority of whom were Hispanic, from a single center were evaluated before and after initiation of TNF antagonist therapy. As controls, 12 RA patients from the same center who were not treated with a TNF antagonist were studied. Plasma type I IFN activity was measured using a reporter cell assay, and disease status was assessed using the Disease Activity Score in 28 joints (DAS28). Levels of interleukin-1 receptor antagonist (IL-1Ra) were determined in baseline plasma samples using a commercial enzyme-linked immunosorbent assay. The clinical response was classified according to the European League Against Rheumatism criteria for improvement in RA.



Plasma type I IFN activity at baseline was significantly associated with clinical response (odds ratio 1.36 [95% confidence interval 1.05-1.76], P = 0.020), with high baseline IFN activity associated with a good response. Changes in DAS28 scores were greater among patients with a baseline plasma IFNbeta/alpha ratio >0.8 (indicating elevated plasma IFNbeta levels). Consistent with the capacity of IFNbeta to induce IL-1Ra, elevated baseline IL-1Ra levels were associated with better therapeutic outcomes (odds ratio 1.82 [95% confidence interval 1.1-3.29], P = 0.027).



The plasma type I IFN activity, the IFNbeta/alpha ratio, and the IL-1Ra level were predictive of the therapeutic response in TNF antagonist-treated RA patients, indicating that these parameters might define clinically meaningful subgroups of RA patients with distinct responses to therapeutic agents.
An instrument for measuring health-related quality of life in patients with Deep Venous Thrombosis (DVT): development and validation of Deep Venous Thrombosis Quality of Life (DVTQOL) questionnaire

Few studies have evaluated patient-reported outcomes in connection with a primary event of deep venous thrombosis, partly due to a lack of disease-specific measures. The aim here was to develop a disease-specific health-related quality of life (HRQL) measure, the deep venous thrombosis quality of life questionnaire (DVTQOL), for patients with recent exposition and treatment of proximal deep venous thrombosis.



A total of 121 consecutive outpatients (50 % males; mean age 61.2 +/- 14 years) treated with warfarin (Waran) for symptomatic proximal deep venous thrombosis were included in the study. Patients completed the SF-36, EQ-5D and the pilot version of the DVTQOL.



Items having: high ceiling and floor effect, items with lower factor loadings than 0.50 and items loading in several factors were removed from the pilot version of DVTQOL. In addition, overlapping and redundant items identified by the Rasch analysis were excluded. The final DVTQOL questionnaire consists of 29 items composing six dimensions depicting problems with: emotional distress; symptoms (e.g. pain, swollen ankles, cramp, bruising); limitation in physical activity; hassle with coagulation monitoring; sleep disturbance; and dietary problems. The internal consistency reliability was high (alpha value ranged from 0.79 to 0.93). The relevant domains of the SF-36 and EQ-5D significantly correlated with DVTQOL, thereby confirming its construct validity.



The DVTQOL is a short and user-friendly instrument with good reliability and validity. Its test-retest reliability and responsiveness to change in clinical trials, however, must be explored.
Association between anti-tumour necrosis factor treatment response and genetic variants within the TLR and NF{kappa}B signalling pathways.

To determine whether genetic variation within genes integral to the Toll-like receptor (TLR) and NFkappaB signalling systems, two cardinal regulators of inflammatory and immune responses, contributes towards the observed variation in response to tumour necrosis factor (TNF) blocking agents in patients with rheumatoid arthritis (RA).



Pairwise-tagging single nucleotide polymorphisms (SNPs) spanning 24 candidate genes were selected and genotyped in a large UK cohort of patients receiving anti-TNF therapy for RA. Multivariate regression analyses were performed to test association between individual genotypes, under an additive model, and treatment response at 6 months' follow-up assessed using both the absolute change in 28-joint count Disease Activity Score (DAS28) and the European League Against Rheumatism (EULAR) response criteria. Analyses were performed across subgroups comprising etanercept-, infliximab- and infliximab/adalimumab-treated patients as well as the combined anti-TNF-treated cohort. p Values <0.05 were considered statistically significant.



A total of 187 SNPs were successfully genotyped and analysed in 909 patients. Eight SNPs spanning six genes demonstrated nominal evidence of association with response (DAS28) across the anti-TNF-treated subgroups, six of which were restricted to etanercept-treated patients. Twelve SNPs spanning nine genes demonstrated nominal evidence of association with treatment response (DAS28 and/or EULAR) across the combined anti-TNF cohort. These included SNPs mapping to MyD88 (rs7744) and CHUK (rs11591741), which were associated under each model applied (etanercept-treated and combined anti-TNF cohort analysis (DAS28 and EULAR)).



Several SNPs mapping to the TLR and NFkappaB signalling systems demonstrated association with anti-TNF response as a whole and, in particular, with response to etanercept. Validation of these findings in an independent cohort is now warranted.
The insulin sensitiser pioglitazone does not influence skin microcirculatory function in patients with type 2 diabetes treated with insulin

Insulin resistance is associated with abnormal microvascular function. Treatment with insulin sensitisers may provoke oedema, suggesting microvascular effects. The mechanisms underlying the peripheral oedema observed during glucose-lowering treatment with thiazolidinediones are unclear. Therefore we examined the effect of pioglitazone on microvascular variables involved in oedema formation. Subjects (40–80 years) with type 2 diabetes and on insulin were randomised to 9 weeks of pioglitazone therapy (30 mg/day; n=14) or placebo (n=15). The following assessments were performed at baseline and 9 weeks: microvascular filtration capacity; isovolumetric venous pressure; capillary pressure; capillary recruitment following venous or arterial occlusion; postural vasoconstriction; and maximum blood flow. A number of haematological variables were also measured including vascular endothelium growth factor (VEGF), IL-6 and C-reactive protein (CRP). Pioglitazone did not significantly influence any microcirculatory variable as compared with placebo (analysis of covariance [ANCOVA] for microvascular filtration capacity for the two groups, p=0.26). Mean VEGF increased with pioglitazone (61.1 pg/ml), but not significantly more than placebo (9.76 pg/ml, p=0.94). HbA1c levels and the inflammatory markers IL-6 and CRP decreased with pioglitazone compared with placebo (ANCOVA: p=0.009, p=0.001 and p=0.004, respectively). Pioglitazone improved glycaemic control and inflammatory markers over 9 weeks but had no effect on microcirculatory variables associated with oedema or insulin resistance in type 2 diabetic patients treated with insulin.
Randomised comparison of the effects of nicardipine and esmolol on coronary artery wall stress: implications for the risk of plaque rupture.

To determine whether the beta blocker esmolol reduces coronary artery wall stress more than the short acting dihydropyridine calcium antagonist nicardipine.



Randomised double blind placebo controlled trial.



Tertiary cardiology centre.



Patients with coronary artery disease.



20 patients were randomised double blind to an infusion of nicardipine (n = 10) or esmolol (n = 10) titrated to reduce systolic blood pressure by 20 mm Hg.



Peak systolic wall circumferential stress.



Esmolol reduced peak coronary stress by a mean of 0.17 x 10(6) dyn/cm(2) (95% confidence interval (CI) 0.14 to 0.21 x 10(6) dyn/cm(2)) compared with a reduction of 0.07 x 10(6) dyn/cm(2) (95% CI 0.05 to 0.10 x 10(6) dyn/cm(2)) after nicardipine. Peak systolic radius was reduced by 0.04 mm (95% CI 0.03 to 0.06 mm) after esmolol compared with an increase of 0.08 mm (95% CI 0.05 to 0.10 mm) after nicardipine. Heart rate increased by 11.5 beats/min (95% CI 6.9 to 16.2 beats/min) after nicardipine and decreased by 5.3 beats/min (95% CI 1.9 to 8.6 beats/min) after esmolol.



Intravenous esmolol is more effective than nicardipine at reducing circumferential coronary artery wall stress.
andidate Gene Polymorphisms in the Serotonergic athway : Influence on Depression Symptomatology n an Elderly Population

ackground: Depressed mood is a major concern in the elderly, with consequences for morbidity and mortality. Previous studies have emonstrated that genetic factors in depression and subsyndromal depressive symptoms are no less important in the elderly than uring other life stages. Variations in genes included in the serotonin system have been suggested as risk factors for various psychiatric isorders but may also serve as candidates for normal variations in mood.  This study included 684 elderly Danish twins to investigate the influence of 11 polymorphisms in 7 serotonin system genes n the mean level of depression symptomatology assessed over several years, reflecting individuals’ underlying mood level.  A suggestive association of sequence variations in genes responsible for the synthesis (TPH), recognition (5-HTR2A), and egradation (MAOA) of serotonin with depression symptomatology was found, although the effect was generally restricted to men. We lso found that a specific haplotype in VMAT2, the gene encoding the vesicular monoamine transporter, was significantly associated ith depression symptoms in men (p .007).  These results suggest that variations in genes encoding the components of serotonin metabolism may influence the basic ood level and that different genetic factors may apply in men and women.
The secret life of bugs: Going past the errors and omissions in software repositories

Every bug has a story behind it. The people that discover and resolve it need to coordinate, to get information from documents, tools, or other people, and to navigate through issues of accountability, ownership, and organizational structure. This paper reports on a field study of coordination activities around bug fixing that used a combination of case study research and a survey of software professionals. Results show that the histories of even simple bugs are strongly dependent on social, organizational, and technical knowledge that cannot be solely extracted through automation of electronic repositories, and that such automation provides incomplete and often erroneous accounts of coordination. The paper uses rich bug histories and survey results to identify common bug fixing coordination patterns and to provide implications for tool designers and researchers of coordination in software development.
Mediators and moderators of the effects of a year-long exercise intervention on endogenous sex hormones in postmenopausal women

To identify factors that mediate or moderate the effects of exercise on postmenopausal sex hormone concentrations. Postmenopausal women were randomized to 12 months of aerobic exercise for 200 min/week (n = 160) or to a control group (n = 160). Intention-to-treat analyses were performed using general linear models with sex hormone concentrations at 6 and 12 months as the outcome. Mediation by adiposity and insulin was investigated by examining changes in effect estimates after adjustment for changes in these factors over 12 months. Moderation was studied as the interaction between group assignment and eight baseline characteristics. Intervention effects on sex hormone–binding globulin (SHBG) and estradiol changes were attenuated with adjustment for change in overall body fat, while there was less attenuation adjusting for intra-abdominal fat change. Intervention effects on SHBG levels were unaffected by adjustment for insulin change. Significant interactions were identified between treatment and physical fitness (for SHBG and testosterone) and age (for testosterone), implying subgroup differences in intervention effect. Our data suggest that overall fat loss partially mediated exercise-induced changes in estradiol and SHBG concentrations. No previous RCT in postmenopausal women has studied moderators of exercise-induced sex hormone changes; therefore, future studies are needed to corroborate our results.
Automatic Segmentation of Intra-treatment CT Images for Adaptive Radiation Therapy of the Prostate

We have been developing an approach for automatically quantifying organ motion for adaptive radiation therapy of the prostate. Our approach is based on deformable image registration, which makes it possible to establish a correspondence between points in images taken on different days. This correspondence can be used to study organ motion and to accumulate inter-fraction dose. In prostate images, however, the presence of bowel gas can cause significant correspondence errors. To account for this problem, we have developed a novel method that combines large deformation image registration with a bowel gas segmentation and deflation algorithm. In this paper, we describe our approach and present a study of its accuracy for adaptive radiation therapy of the prostate. All experiments are carried out on 3-dimensional CT images.