nils-herrmann/clean_scirepeval huggingface dataset:
A phase I trial of flavopiridol in relapsed multiple myeloma

Flavopiridol is primarily a cyclin-dependent kinase-9 inhibitor, and we performed a dose escalation trial to determine the maximum tolerated dose and safety and generate a pharmacokinetic (PK) profile. Patients with a diagnosis of relapsed myeloma after at least two prior treatments were included. Flavopiridol was administered as a bolus and then continuous infusion weekly for 4 weeks in a 6-week cycle. Fifteen patients were treated at three dose levels (30 mg/m2 bolus, 30 mg/m2 CIV to 50 mg/m2 bolus, and 50 mg/m2 CIV). Cytopenias were significant, and elevated transaminases (grade 4 in 3 patients, grade 3 in 4 patients, and grade 2 in 3 patients) were noted but were transient. Diarrhea (grade 3 in 6 patients and grade 2 in 5 patients) did not lead to hospital admission. There were no confirmed partial responses although one patient with t(4;14) had a decrease in his monoclonal protein >50 % that did not persist. PK properties were similar to prior publications, and immunohistochemical staining for cyclin D1 and phospho-retinoblastoma did not predict response. Flavopiridol as a single agent given by bolus and then infusion caused significant diarrhea, cytopenias, and transaminase elevation but only achieved marginal responses in relapsed myeloma (ClinicalTrials.gov identifier NCT00112723).
Intravenous recombinant human relaxin in compensated heart failure: a safety, tolerability, and pharmacodynamic trial.

Relaxin is upregulated in human heart failure (HF). Animal and clinical data suggest beneficial hemodynamic and renal effects from vasodilation. We determined safety, tolerability, and pharmacodynamic effects of human Relaxin in stable HF.



Sixteen patients were treated with open-label intravenous Relaxin in 3 dose-escalation cohorts and monitored hemodynamically for 24-hour infusion and postinfusion periods and followed until Day 30. The safety demonstrated in Group A (8-hour sequential infusions at dose levels of 10, then 30, and then 100 microg x kg x day equivalents) allowed escalation to Group B (240, 480, and 960 microg x kg x day). The highest safe dose, 960 microg x kg x day, was selected for a 24-hour infusion in Group C. Relaxin showed no adverse effects; produced hemodynamic effects consistent with vasodilation (ie, trends toward increases in cardiac index, decreases in pulmonary wedge pressure, and decreases in circulating NT-pro BNP without inducing hypotension; improved markers of renal function [creatinine, blood urea nitrogen]). The highest dose caused a transient elevation in creatinine and blood urea nitrogen at Day 9 that was without apparent clinical significance.



Relaxin was safe and well-tolerated in patients with stable HF, and preliminary pharmacodynamic responses suggest it causes vasodilation. Further evaluation of the safety and efficacy of this drug in HF appears warranted.
Quality of life is associated with physical activity and fitness in cystic fibrosis

Health-related and disease-specific quality of life (HRQoL) has been increasingly valued as relevant clinical parameter in cystic fibrosis (CF) clinical care and clinical trials. HRQoL measures should assess - among other domains - daily functioning from a patient's perspective. However, validation studies for the most frequently used HRQoL questionnaire in CF, the Cystic Fibrosis Questionnaire (CFQ), have not included measures of physical activity or fitness. The objective of this study was, therefore, to determine the cross-sectional and longitudinal relationships between HRQoL, physical activity and fitness in patients with CF.



Baseline (n = 76) and 6-month follow-up data (n = 70) from patients with CF (age ≥12 years, FEV1 ≥35%) were analysed. Patients participated in two multi-centre exercise intervention studies with identical assessment methodology. Outcome variables included HRQoL (German revised multi-dimensional disease-specific CFQ (CFQ-R)), body composition, pulmonary function, physical activity, short-term muscle power, and aerobic fitness by peak oxygen uptake and aerobic power.



Peak oxygen uptake was positively related to 7 of 13 HRQoL scales cross-sectionally (r = 0.30-0.46). Muscle power (r = 0.25-0.32) and peak aerobic power (r = 0.24-0.35) were positively related to 4 scales each, and reported physical activity to 1 scale (r = 0.29). Changes in HRQoL-scores were directly and significantly related to changes in reported activity (r = 0.35-0.39), peak aerobic power (r = 0.31-0.34), and peak oxygen uptake (r = 0.26-0.37) in 3 scales each. Established associates of HRQoL such as FEV1 or body mass index correlated positively with fewer scales (all 0.24 < r < 0.55).



HRQoL was associated with physical fitness, especially aerobic fitness, and to a lesser extent with reported physical activity. These findings underline the importance of physical fitness for HRQoL in CF and provide an additional rationale for exercise testing in this population.
Evaluation of adjunctive systemic doxycycline with non-surgical periodontal therapy within type 2 diabetic patients

To evaluate the effects of systemic doxycycline on clinical and microbiological parameters of diabetic subjects with chronic periodontitis.



This 9-month multi-center, randomized, parallel, single-blinded study was conducted from different hospitals in Riyadh, Saudi Arabia between April 2010 and December 2010. A total of 76 diabetic subjects with chronic periodontitis were randomized into 2 groups: control group (CG) received only scaling and root planing (SRP), and the treatment group (TG) receiving systemic doxycycline during the reevaluation visit 45 days after the completion of SRP. Probing pocket depth, clinical attachment level, gingival index, plaque index, and bleeding on probing were collected at baseline, 45 days after SRP, and one, 3, and 6 months  after the use of systemic doxycycline. Microbiological analysis comprised the detection of Tannerella forsythia (Tf), Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), and Prevotella intermedia (Pi) by polymerase chain reaction method.



Sixty-eight (33 CG and 35 TG) subjects completed the study. Greater reduction in the population of Tf, Pg, and Pi were observed in TG compared with CG in the first month after the administration of systemic doxycycline. The TG showed a significant improvement in gingival index scores compared with the CG (p<0.05) by the end of the first and 6 months after the administration of doxycycline.



Adjunct systemic doxycycline can be associated with a reduction of Tf, Pg, and Pi in the first month after the administration of doxycycline with an improvement in the GI.
Characteristics of prevalent and new COPD cases in Greece: the GOLDEN study

Greece has one of the highest rates of smoking and chronic obstructive pulmonary disease (COPD) in Europe.



The study aimed to record both the disease characteristics among a sample of Greek COPD patients and the nationwide rates of newly diagnosed COPD cases.



In this noninterventional, epidemiological cross-sectional study, a representative nationwide sample of 45 respiratory centers provided data on the following: 1) the demographic and clinical characteristics of COPD patients and 2) newly diagnosed COPD cases monitored over a period of 6 months by each physician.



Data from 6,125 COPD patients were collected. Advanced age (median age: 68 years), male predominance (71.3%), largely overweight status with median body mass index (BMI) =27.5 kg/m(2), high percentage of current and ex-smokers (89.8%), and presence of comorbidities (81.9%) were evident in the sample. According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 criteria, majority of the COPD patients had moderate or severe airflow limitation (61%). Severity of airflow limitation was significantly associated with older age, male sex, obesity, ex-smoking status, and presence of comorbidity (all P-values <0.001). A total of 61.3% of the patients received medication, mostly bronchodilators (64.4%) and fixed-dose combinations of long-acting β2-agonists and inhaled corticosteroids (39.9%), while 35.9% reported taking medication on demand. The majority (81.1%) of patients reported a preference for fewer inhalations of their bronchodilator therapy. Based on the mixed-effect Poisson model, the rate of newly diagnosed COPD cases was estimated to be 18.2% (95% confidence interval: 14.9-22.3) per pulmonologist/3 months. Of those newly diagnosed, the majority of patients had mild or moderate airflow limitation (78.2%).



The Greek Obstructive Lung Disease Epidemiology and health ecoNomics study reflected the real-life profile of COPD patients and provided evidence on the profile of new COPD cases in Greece. Various demographic factors were delineated, which can assist in designing more effective diagnostic and management strategies for COPD in Greece.
Periprosthetic bone remodelling of two types of uncemented femoral implant with proximal hydroxyapatite coating: a 3-year follow-up study addressing the influence of prosthesis design and preoperative bone density on periprosthetic bone loss

Periprosthetic bone loss is a major cause of concern in patients undergoing total hip arthroplasty (THA). Further studies are required to identify the factors determining the pattern of bone remodelling following THA and obtain improvements in the design and durability of prostheses. In this study, we monitored periprosthetic bone loss around two different types of hydroxyapatite coated femoral implant over a 3-year period to evaluate their design and investigate the relationship with the preoperative bone mineral density (BMD) at the spine, hip and forearm. Sixty patients (35 F, 25 M, mean age 63 years, range 46–75 years) undergoing THA were randomised to either the Anatomic Benoist Girard (ABG) or Mallory-Head (MH) femoral stem. Preoperative dual-energy X-ray absorptiometry (DXA) scans were acquired of the posteroanterior (PA) and lateral lumbar spine, the contralateral hip and the non-dominant forearm. Postoperative DXA scans were performed to measure periprosthetic BMD at 10 days (treated as baseline), 6 weeks, and 3, 6, 12, 24 and 36 months after THA using a standard Gruen zone analysis. Results were expressed as the percentage change from baseline and the data examined for the differences in bone loss between the different Gruen zones, between the ABG and MH stems, and the relationship with preoperative BMD. A total of 50 patients (24 ABG, 26 MH) completed the study. Three months after THA there was a statistically significant BMD decrease in every Gruen zone that varied between 5.6% and 13.8% for the ABG prosthesis and between 3.8% and 8.7% for the MH prosthesis. Subsequently, in most zones BMD reached a plateau or showed a small recovery. However, BMD continued to fall in Gruen zones 1 and 7 in ABG patients and Gruen zone 1 in MH patients. Bone loss was less in every Gruen zone in MH patients compared with ABG with the largest difference (10%, P=0.018) in Gruen zone 7. Highly significant relationships were found between periprosthetic bone loss and preoperative BMD measured at the PA spine (P<0.001), total hip (P=0.004) and total distal radius (P<0.001). This study showed differences between two different designs of hydroxyapatite-coated implant that confirmed that prosthesis design influences periprosthetic bone loss. The study also showed that patients’ bone density measured at the spine, hip or forearm at the time of operation was a major factor influencing bone loss around the femoral stem.
Genetic and environmental influences on the prospective correlation between systemic inflammation and coronary heart disease death in male twins.

Because of lack of evidence, we aimed to examine to what degree low-grade systemic inflammation and coronary heart disease (CHD) death shared common genetic and environmental substrates.



From the 41-year prospective National Heart, Lung, and Blood Institute Twin Study, we included 950 middle-aged male twins at baseline (1969-1973). Low-grade systemic inflammation was measured with plasma levels of interleukin-6 (IL-6) and C-reactive protein. Univariate and bivariate structural equation models were used, adjusted for a risk score for CHD death. The score-adjusted heritability was 19% for IL-6, 27% for C-reactive protein, and 22% for CHD death. The positive phenotypic correlation of IL-6 with CHD death (radjusted=0.27; 95% confidence interval [CI], 0.08-0.43) was driven by additive genetic factors (contribution [relative contribution], 0.30 [111%]) but attenuated by unique environment (-0.03 [-11%]). The genetic correlation between IL-6 and CHD death was 0.74 (95% CI, 0.21-1.00), whereas the unique environmental correlation was -0.05 (95% CI, -0.35 to 0.25). The proportion of genetic variance for CHD death shared with that for IL-6 was 74%. The phenotypic correlation of C-reactive protein with CHD death (radjusted=0.10; 95% CI, -0.02 to 0.22) was explained by additive genetic factors (0.20 [149%]) but was attenuated by the unique environment (-0.09 [-49%]). The genetic correlation of C-reactive protein with CHD death was 0.63 (95% CI, -0.07 to 1.00), whereas the unique environmental correlation was -0.07 (95% CI, -0.29 to 0.17).



Low-grade systemic inflammation, measured by IL-6, and long-term CHD death share moderate genetic substrates that augment both traits.
Acceptability and outcomes of percutaneous endoscopic gastrostomy (PEG) tube placement and patient quality of life.

Since its description in 1980, percutaneous endoscopic gastrostomy has been a widely used method for insertion of a gastrostomy tube in patients who are unable to swallow or maintain adequate nutrition. This study aimed to assess the perspectives of patients/caregivers in our society regarding the acceptability of percutaneous endoscopic gastrostomy tube placement and to evaluate the outcomes.



One hundred consecutive adults referred to our unit to be considered for primary percutaneous endoscopic gastrostomy feeding at Imam Reza Hospital of Tabriz University of Medical Sciences were evaluated prospectively from October 2007 to June 2009. The nutritional status of patients, complications and quality of life were assessed after percutaneous endoscopic gastrostomy insertion for six months. The data were analyzed using SPSS software.



Indications for percutaneous endoscopic gastrostomy were neurologic in 66 patients and recurrent pulmonary aspiration in 14 intensive care unit adult patients. Minor complications included percutaneous endoscopic gastrostomy site infection in 8 patients and tube blockage in 5 patients. Oral feeding was resumed in 27% of the patients and the tube was removed subsequently after 3-6 months; 42 patients died due to primary diseases (in 1-6 months). The Quality of Life Index scores pre-percutaneous endoscopic gastrostomy placement and 6 months after percutaneous endoscopic gastrostomy averaged 19.25±11.85 and 30.08±27.74, respectively. A similarly significant difference was also found between mean Quality of Life Index scores pre- and post-percutaneous endoscopic gastrostomy placement (p<0.005).



Percutaneous endoscopic gastrostomy is a minimally invasive gastrostomy method with low morbidity and mortality rates, and is easy to follow-up and to replace when blockage occurs.
Measurement-calibrated graph models for social network experiments

Access to realistic, complex graph datasets is critical to research on social networking systems and applications. Simulations on graph data provide critical evaluation of new systems and applications ranging from community detection to spam filtering and social web search. Due to the high time and resource costs of gathering real graph datasets through direct measurements, researchers are anonymizing and sharing a small number of valuable datasets with the community. However, performing experiments using shared real datasets faces three key disadvantages: concerns that graphs can be de-anonymized to reveal private information, increasing costs of distributing large datasets, and that a small number of available social graphs limits the statistical confidence in the results.
 The use of measurement-calibrated graph models is an attractive alternative to sharing datasets. Researchers can "fit" a graph model to a real social graph, extract a set of model parameters, and use them to generate multiple synthetic graphs statistically similar to the original graph. While numerous graph models have been proposed, it is unclear if they can produce synthetic graphs that accurately match the properties of the original graphs. In this paper, we explore the feasibility of measurement-calibrated synthetic graphs using six popular graph models and a variety of real social graphs gathered from the Facebook social network ranging from 30,000 to 3 million edges. We find that two models consistently produce synthetic graphs with common graph metric values similar to those of the original graphs. However, only one produces high fidelity results in our application-level benchmarks. While this shows that graph models can produce realistic synthetic graphs, it also highlights the fact that current graph metrics remain incomplete, and some applications expose graph properties that do not map to existing metrics.
Clinical characteristics of patients with bronchioloalveolar carcinoma: a retrospective study of 44 cases.

Bronchioloalveolar carcinoma (BAC) is considered a subtype of adenocarcinoma of the lung. Recently BAC has been variously termed adenocarcinoma in situ, minimally invasive adenocarcinoma, lepidic predominant invasive adenocarcinoma, and invasive mucinous adenocarcinoma. The aim of the study was to analyze and detect prognostic factors of patients with BAC over a 7-year period.



This retrospective single-center study included 44 patients with BAC. The impact on survival of fifteen variables (gender, age, smoking status, cough, dyspnea, hemoptysis, fever, chest pain, sputum, metastasis number, Karnofsky performance status, pT, pN, TNM stage, cytotoxic chemoterapy) were assessed.



Median age was 55 years (38-83). Most patients were male (63.6%) and stage IV (59.1%). Twenty-one patients (47.7%) received cytotoxic chemotherapy (platinum-based regimens) for metastatic disease. Objective response rate was 33.3% (4 partial, 3 complete responses). Stable disease was observed in nine in patients (42.8%). Disease progression was noted in 5 (23.8%). The median OS for all patients was 12 months (95%CI, 2.08-22.9 months). Independent predictors for overall survival were: Karnofsky performance status (HR:3.30, p 0.009), pN (HR:3.81, p 0.018), TNM stage (HR:6.49, p 0.012) and hemoptysis (HR:2.31, p 0.046).



Karnofsky performance status, pN, TNM stage and hemoptysis appear to have significant impact on predicting patient survival in cases of BAC.
Pranlukast, a novel leukotriene receptor antagonist: results of the first European, placebo controlled, multicentre clinical study in asthma.

Leukotriene receptor antagonists have been shown to protect against bronchoconstriction induced by antigens, exercise, and cold air. There are relatively few clinical studies reported in patients with asthma. The present study is the first clinical evaluation of pranlukast (SB 205312, ONO-1078) outside Japan in patients with asthma.



A randomised, double blind, placebo controlled, parallel group, multicentre four week study of the safety and tolerability of oral pranlukast, 225 or 337.5 mg twice daily, was performed in patients with mild to moderate asthma. Preliminary efficacy data were obtained; the main efficacy variables evaluated were forced expiratory volume in one second (FEV1) and morning domiciliary (home) peak expiratory flow rates (PEFR). Clinic PEFR and daytime and night-time asthma symptom scores were also recorded.



Compared with the placebo group the improvement in morning home PEFR was statistically significant at all time points for patients receiving pranlukast 337.5 mg twice daily and at weeks 1 and 2 for those treated with pranlukast in a dose of 225 mg twice daily. Mean morning home PEFR increased by 10.8 to 18.61/min (95% CI 0.2 to 29.3 l/min) in patients treated with pranlukast compared with a slight deterioration in those given placebo. FEV1 significantly increased within one hour after the first dose of pranlukast compared with baseline and this increase was maintained for eight hours. Improvements in trough FEV1-that is, at the end of the dosing interval-were statistically significant for the group treated with pranlukast 225 mg twice daily compared with placebo at week 4. Mean increases in FEV1 ranged from 210 ml to 340 ml (95% CI 60 to 500 ml) at trough in the pranlukast group. Patients treated with pranlukast also showed improvements in summary symptom and night-time asthma scores. Pranlukast was well tolerated, and no drug related changes in haematological and biochemical variables were observed.



Pranlukast, an oral leukotriene receptor antagonist, is well tolerated and is effective for the treatment of asthma. It increased FEV1 within one hour of dosing, improved patient summary symptom and night-time asthma scores, and reduced the use of rescue bronchodilators, thus providing further evidence of a role for leukotrienes in the pathogenesis of asthma.
Mitral valve repair with Carpentier-McCarthy-Adams IMR ETlogix annuloplasty ring for ischemic mitral regurgitation: early echocardiographic results from a multi-center study.

Ischemic mitral regurgitation (IMR) is associated with asymmetric changes in annular and ventricular geometry. Surgical repair with standard symmetric annuloplasty rings results in a high incidence of residual or recurrent mitral regurgitation (MR). The Carpentier-McCarthy-Adams (CMA) IMR ETlogix annuloplasty ring is the first remodeling ring specifically designed to treat asymmetric leaflet tethering and annular dilatation. We used quantitative 2-dimensional echo to examine early results of mitral valve (MV) repair with the CMA IMR ETlogix annuloplasty ring in patients with IMR.



Fifty-nine patients (aged 68+/-12 years) with grade > or = 2+ IMR (graded on a scale of 0 to 4+) underwent MV repair with the CMA IMR ETlogix annuloplasty ring. We assessed the mitral annular diameter (MAD), tethering area (TA), and tenting height (TH) of the MV in 4-chamber, 2-chamber, and long axis views at mid-systole before and 3 to 10 days after surgery. After surgery, 57 of 59 (97%) patients had grade 0 or 1+ MR, whereas 2 patients had 2+ MR. MV repair with the CMA IMR ETlogix ring significantly reduced MAD, TA, and TH (P<0.001, for all 3 echo views), particularly in the long axis and 4-chamber views.



Surgical repair of IMR with the novel asymmetric CMA IMR ETlogix annuloplasty ring provided excellent early results with effective reduction of MR, MAD, and leaflet tethering. This novel etiology-specific strategy may result in improved outcomes in IMR patients.