nils-herrmann/clean_scirepeval huggingface dataset:
Dietary acrylamide intake and the risk of cancer among Finnish male smokers

To assess the association between dietary acrylamide intake and the risk of cancer among male smokers. The study consisted of 27,111 male smokers, aged 50–69 years, without history of cancer. They were participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study in Finland. The men completed a validated dietary questionnaire and a questionnaire on general background characteristics (including smoking habits) at baseline. Incident cases of cancer were identified through the national Finnish Cancer Registry. During an average 10.2 year follow-up, 1,703 lung cancers, 799 prostate cancers, 365 urothelial cancers, 316 colorectal cancers, 224 stomach cancers, 192 pancreatic cancers, 184 renal cell cancers, and 175 lymphomas were diagnosed. Dietary acrylamide intake was positively associated with the risk of lung cancer; relative risk (RR) in the highest versus the lowest quintile in the multivariable-adjusted model was 1.18 ((95% confidence interval (CI) 1.01–1.38, p for trend 0.11). Other cancers were not associated with acrylamide intake. High acrylamide intake is associated with increased risk of lung cancer but not with other cancers in male smokers.
Inherited variants in mitochondrial biogenesis genes may influence epithelial ovarian cancer risk.

Mitochondria contribute to oxidative stress, a phenomenon implicated in ovarian carcinogenesis. We hypothesized that inherited variants in mitochondrial-related genes influence epithelial ovarian cancer (EOC) susceptibility.



Through a multicenter study of 1,815 Caucasian EOC cases and 1,900 controls, we investigated associations between EOC risk and 128 single nucleotide polymorphisms (SNPs) from 22 genes/regions within the mitochondrial genome (mtDNA) and 2,839 nuclear-encoded SNPs localized to 138 genes involved in mitochondrial biogenesis (BIO, n = 35), steroid hormone metabolism (HOR, n = 13), and oxidative phosphorylation (OXP, n = 90) pathways. Unconditional logistic regression was used to estimate OR and 95% CI between genotype and case status. Overall significance of each gene and pathway was evaluated by using Fisher's method to combine SNP-level evidence. At the SNP level, we investigated whether lifetime ovulation, hormone replacement therapy (HRT), and cigarette smoking were confounders or modifiers of associations.



Interindividual variation involving BIO was most strongly associated with EOC risk (empirical P = 0.050), especially for NRF1, MTERF, PPARGC1A, ESRRA, and CAMK2D. Several SNP-level associations strengthened after adjustment for nongenetic factors, particularly for MTERF. Statistical interactions with cigarette smoking and HRT use were observed with MTERF and CAMK2D SNPs, respectively. Overall variation within mtDNA, HOR, and OXP was not statistically significant (empirical P > 0.10).



We provide novel evidence to suggest that variants in mitochondrial biogenesis genes may influence EOC susceptibility.



A deeper understanding of the complex mechanisms implicated in mitochondrial biogenesis and oxidative stress may aid in developing strategies to reduce morbidity and mortality from EOC.
BAX/BCL2 RMFI ratio predicts better induction response in pediatric patients with acute myeloid leukemia.

BAX/BCL2 ratio in pediatric AML has not been evaluated. In this first prospective study, we evaluated BAX/BCL2 transcript and RMFI ratio in 64 patients using real-time PCR (TaqMan Probe chemistry) and flow-cytometry, respectively. There was no correlation of BAX/BCL2 transcript ratio with RMFI ratio (R = -0.05; P = 0.715). Patients with WBC count >50,000/mm(3) had lower BAX/BCL2 RMFI ratio (P = 0.043), whereas no difference in ratio was observed among patients of different cytogenetics subgroups (P = 0.786). Higher BAX/BCL2 RMFI ratio was associated positively with CR rate (P = 0.03), but this study was unable to show that it translated into improved EFS or OS.
Anatomical Network Comparison of Human Upper and Lower, Newborn and Adult, and Normal and Abnormal Limbs, with Notes on Development, Pathology and Limb Serial Homology vs. Homoplasy

How do the various anatomical parts (modules) of the animal body evolve into very different integrated forms (integration) yet still function properly without decreasing the individual's survival? This long-standing question remains unanswered for multiple reasons, including lack of consensus about conceptual definitions and approaches, as well as a reasonable bias toward the study of hard tissues over soft tissues. A major difficulty concerns the non-trivial technical hurdles of addressing this problem, specifically the lack of quantitative tools to quantify and compare variation across multiple disparate anatomical parts and tissue types. In this paper we apply for the first time a powerful new quantitative tool, Anatomical Network Analysis (AnNA), to examine and compare in detail the musculoskeletal modularity and integration of normal and abnormal human upper and lower limbs. In contrast to other morphological methods, the strength of AnNA is that it allows efficient and direct empirical comparisons among body parts with even vastly different architectures (e.g. upper and lower limbs) and diverse or complex tissue composition (e.g. bones, cartilages and muscles), by quantifying the spatial organization of these parts-their topological patterns relative to each other-using tools borrowed from network theory. Our results reveal similarities between the skeletal networks of the normal newborn/adult upper limb vs. lower limb, with exception to the shoulder vs. pelvis. However, when muscles are included, the overall musculoskeletal network organization of the upper limb is strikingly different from that of the lower limb, particularly that of the more proximal structures of each limb. Importantly, the obtained data provide further evidence to be added to the vast amount of paleontological, gross anatomical, developmental, molecular and embryological data recently obtained that contradicts the long-standing dogma that the upper and lower limbs are serial homologues. In addition, the AnNA of the limbs of a trisomy 18 human fetus strongly supports Pere Alberch's ill-named "logic of monsters" hypothesis, and contradicts the commonly accepted idea that birth defects often lead to lower integration (i.e. more parcellation) of anatomical structures.
ATHOME: Automatic Tunable Wireless Charging for Smart Home

We present ATHOME, an Automatic Tunable wireless charging framework for smart low-power devices in current and future HOME. ATHOME automatically tunes the charging power of multiple stationary wireless chargers to provide enough energy that can continuously power up smart devices with varying working power profiles, while minimizing the total charging power to reduce energy cost. To reach this goal, ATHOME first solves a hard open problem of calculating the minimum required charging power for powering up a device with limited energy storage size and varying power profile. Based on the minimum charging power obtained for each device, ATHOME then provides an optimal solution with polynomial-time complexity that automatically tunes the charging power of all chargers in a real-time fashion, which enables all devices to work continuously while minimizing total charging power. We implement ATHOME on a WISP platform with 8 rechargeable nodes. Experiments demonstrate that ATHOME provides sufficient and tight charging power that enables devices to work continuously.
The γ-Secretase Modulator, BMS-932481, Modulates Aβ Peptides in the Plasma and Cerebrospinal Fluid of Healthy Volunteers

The pharmacokinetics, pharmacodynamics, safety, and tolerability of BMS-932481, a γ-secretase modulator (GSM), were tested in healthy young and elderly volunteers after single and multiple doses. BMS-932481 was orally absorbed, showed dose proportionality after a single dose administration, and had approximately 3-fold accumulation after multiple dosing. High-fat/caloric meals doubled the Cmax and area under the curve and prolonged Tmax by 1.5 hours. Consistent with the preclinical pharmacology of GSMs, BMS-932481 decreased cerebrospinal fluid (CSF) Aβ39, Aβ40, and Aβ42 while increasing Aβ37 and Aβ38, thereby providing evidence of γ-secretase enzyme modulation rather than inhibition. In plasma, reductions in Aβ40 and Aβ42 were observed with no change in total Aβ; in CSF, modest decreases in total Aβ were observed at higher dose levels. Increases in liver enzymes were observed at exposures associated with greater than 70% CSF Aβ42 lowering after multiple dosing. Although further development was halted due to an insufficient safety margin to test the hypothesis for efficacy of Aβ lowering in Alzheimer's disease, this study demonstrates that γ-secretase modulation is achievable in healthy human volunteers and supports further efforts to discover well tolerated GSMs for testing in Alzheimer's disease and other indications.
Phase 2 and pharmacodynamic study of oral forodesine in patients with advanced, fludarabine-treated chronic lymphocytic leukemia.

Forodesine is a new and potent purine nucleoside phosphorylase (PNP) inhibitor. Patients with chronic lymphocytic leukemia (CLL) with primary resistance to fludarabine-based therapy or with progressive disease were eligible for oral forodesine (200 mg/d) for up to 24 weeks. Eight patients with median lymphocyte count of 35.9 x 10(9)/L and median serum beta2 microglobulin level of 6.45 mg/L were treated. Six had Rai stage III to IV and were previously heavily treated (median prior therapy = 5). Two had transient decrease in lymphocyte count to normal, whereas in 5, disease progressed. Adverse events were mild. Steady-state level of forodesine ranged from 200 to 1300 nM and did not reach desired 2 microM level. PNP inhibition ranged from 57% to 89% and steady-state 2'-deoxyguanosine (dGuo) concentration median was 1.8 microM. Intracellular deoxyguanosine triphosphate (dGTP) increase was very modest, from median of 6 microM to 10 microM. Compared with in vivo, in vitro incubations of CLL lymphocytes with 10 or 20 microM dGuo and forodesine (2 microM) resulted in accumulation of higher levels of dGTP (40-250 microM) which resulted in increase in apoptosis. Forodesine has biologic activity in CLL; pharmacodynamic parameters suggest that an alternate dosing schedule and/or higher doses to achieve greater intracellular dGTP may be beneficial in this patient population.
Examining unidimensionality and improving reliability for the eight subscales of the SF-36 in opioid-dependent patients using Rasch analysis

The Medical Outcome Study Short Form 36 (SF-36) is one of the most commonly used questionnaires for monitoring the Health-Related Quality of Life (HRQOL) of opioid-dependent patients. However, the unidimensionality and reliability of the SF-36 have not been verified in opioid-dependent patients. The aim of this study was to examine the unidimensionality and to improve the test reliability of the SF-36 for use in opioid-dependent patients. A total of 583 opioid-dependent patients were recruited in the study. Unidimensionality was examined by conducting unidimensional Rasch analysis. Item fit statistics and principle component analysis were used to check the item-model fit in each of the eight subscales of the SF-36. Reliability was evaluated by applying both unidimensional and multidimensional Rasch analyses. After three misfitting items were excluded, the remaining items of each subscale in the SF-36 represented a single construct. The test reliabilities (0.80–0.87) yielded by the multidimensional approach were much higher than those (0.68–0.82) produced by the unidimensional approach. The remaining 32 items of the SF-36 are appropriate for evaluating the HRQOL in opioid-dependent patients in terms of unidimensionality. Additionally, the test scores produced by the multidimensional approach were more accurate than those obtained by the unidimensional approach.
Changes in cerebral vessels during experimental hyperlipidemia

Both specific (lipid deposition in endotheliocytes, myocytes, and pericytes) and non-specific (intense formation of apical processes and vacuoles in endotheliocytes and vacuolization of myocytes) changes in cerebral vessels of different diameter were revealed in rabbits and rats after 4 months of experimental hyperlipidemia. These changes suggest reduced endothelium athrombogeneity and intensified transendothelial transport. Biochemical and morphological manifestations of hyperlipidemia in rabbits were more pronounced than in rats.
Intravenous omeprazole rapidly raises intragastric pH.

Twenty four hour intragastric acidity was measured in five duodenal ulcer patients studied at least three times. The effects of different dosage regimens of intravenous omeprazole was compared with placebo. Mean intragastric acidity from 1000 to 0800 was 34.3 +/- 4.3 mmol/l on placebo. After omeprazole 80 mg at 0900 and 40 mg at 1700 mean acidity was 2.1 +/- 0.9 mmol/l and after omeprazole 80 mg at 0900 and 80 mg at 1700 it was 0.7 +/- 0.2 mmol/l. pH remained above 4.0 for about 80% of recordings with these regimens and for only 5% with placebo. Three of the five patients also received omeprazole 80 mg at 0900, 40 mg at 1700 and 40 mg at 0100 when pH remained above 4.0 for 90% of recordings with 99% inhibition of acidity. Omeprazole rapidly raised intragastric pH in all patients and maintained a gastric pH of greater than 4.0 for most of the time. Large doses of IV omeprazole were required compared with studies using the oral compound.
The effect of body position on arterial oxygen saturation in acute stroke.

Evidence suggests that respiratory function is impaired poststroke. Body position is known to influence respiratory function in normal subjects and those with respiratory pathologies. Its effect on respiratory function after stroke has received little attention. However, one study suggests that some positions used in clinical practice may adversely influence respiratory function. This study therefore aimed to identify resting positions that maintain arterial oxygen saturation (SaO2) at optimal levels, changes in SaO2 during time spent in the test position, and differences in SaO2 among the positions investigated.



A within-subject, two-center clinical study was made. Patients in the first 72 hours following mild to moderately severe stroke were allocated a randomized sequence of four positions. One hour was spent in each position. SaO2 was recorded each minute by pulse oximetry with a finger probe. Mean values for the hour were calculated.



Mean arterial oxygen saturation values for all patients were >90% for the hour spent in each test position for all patients. There were no changes in arterial oxygen saturation across the hour spent in the test positions (repeated-measures analysis of variance). No differences in arterial oxygen saturation were identified among positions (analysis of covariance).



The saturation levels recorded corresponded to those observed in studies of normal elderly persons. The positions tested may be recommended for use in clinical practice to maintain arterial oxygen saturation in patients in the first 72 hours following mild to moderately severe stroke.
Effect of whole-body vibration on muscle strength and balance in diplegic cerebral palsy: a randomized controlled trial.

The purpose of this study was to investigate the effects of whole-body vibration training on muscle strength and balance in children with diplegic cerebral palsy.



Fifteen children were assigned to the experimental group, which received whole-body vibration training (9 mins per day, 5 days per week). Another 15 were assigned to the control group, which participated in a traditional physical therapy exercise program for 3 successive months. Baseline and posttreatment assessments were performed using the Biodex isokinetic dynamometer to evaluate the knee extensors peak torque at 60 degrees per second and 90 degrees per second and using the Biodex balance system to evaluate stability index.



The children in the experimental group showed a significant improvement when compared with those in the control group (P < 0.001). The peak torque at 60 degrees per second and 90 degrees per second after treatment was 28.8 ± 0.45 and 47.5 ± 0.7 N · m and 30.9 ± 0.68 and 54.2 ± 1.7 N · m for the control and the experimental group, respectively. The overall stability index after treatment was 2.75 and 2.2 for the control group and the experimental group, respectively.



Whole-body vibration training may be a useful tool for improving muscle strength and balance in children with diplegic cerebral palsy.
Effects of teriparatide in Japanese and non-Japanese populations: bridging findings on pharmacokinetics and efficacy

Teriparatide is an anabolic therapy for osteoporosis approved in the United States since 2002 and European Union since 2003; however, approval in Japan lagged significantly. This report describes analyses based on International Conference on Harmonisation (ICH) E-5 guidelines that support bridging between Japanese studies and the large Fracture Prevention Trial (FPT). We analyzed data from single teriparatide doses in healthy Japanese and Caucasian postmenopausal women (J-PK) and from studies of 6 months [Phase 2, dose ranging (J-Ph2)] and 12 months [Phase 3, efficacy and safety (J-Ph3)] of randomized, placebo-controlled, once-daily treatment in Japanese subjects with osteoporosis. In J-PK, apparent teriparatide area-under-the-curve (AUC) and peak concentration (C max) were up to 40% higher in Japanese versus Caucasian women; however, body weight-adjusted values were comparable between populations; these findings were supported by population pharmacokinetic analyses. Between the FPT and Japanese studies, baseline demographic characteristics were similar but bone mineral density (BMD) at lumbar spine (L1–L4) and body weight were lower for Japanese subjects. With teriparatide 20 μg/day, significant increases in BMD were observed compared to placebo at 12 months in both the FPT and J-Ph3 study, and percent change and actual change in BMD were comparable between studies. Dose response at 6 months was also comparable across populations. No novel safety signals were identified in Japanese subjects. These analyses show that teriparatide clinical data met ICH E-5 criteria for bridging. Findings from foreign trials such as the FPT can thus be extrapolated to Japanese subjects treated with teriparatide 20 μg/day.
Increased serum levels of lipogenic enzymes in patients with severe liver steatosis

Lipid metabolism is altered in subjects with liver steatosis. FAS is a key enzyme in de novo lipogenesis and both FAS gene expression and enzymatic activity are primarily regulated by metabolic signals in the liver. Lipoprotein lipase (LPL), the rate-limiting enzyme for the hydrolysis of core triglycerides, plays a pivotal role in lipid metabolism. This study aims to investigate if circulating levels of FAS and LPL could be clinically associated with liver steatosis. In this work, we present data obtained from a subsample of 94 subjects with liver steatosis enrolled by NUTRIEPA study, a nutritional trial in subjects with liver steatosis. Serum levels of FAS protein and LPL activity were evaluated by ELISA test and by a fluorescent method, respectively. The diagnosis and the degree of liver steatosis were based on laboratory and ecographic measurements. Statistical methods included Kruskal-Wallis analysis of variance and Wilcoxon signed-rank test, where appropriate. The χ2 test has been performed to analyse categorical variables. The subjects with severe steatosis had significantly higher serum levels of FAS protein and LPL activity compared to subjects with mild and moderate liver steatosis. Moreover, a positive trend in serum levels of FAS expression from lower to higher degree of steatosis was also detected. We describe a relationship between human liver steatosis and elevated levels of circulating lipogenic enzymes. Increased serum levels of FAS expression and LPL activity could be considered a marker of severe liver steatosis.
Memantine and brain atrophy in Alzheimer's disease: a 1-year randomized controlled trial.

The primary objective of this study was to evaluate the rate of total brain atrophy (TBA) with serial magnetic resonance imaging (MRI), using the Brain Boundary Shift Integral (BBSI), in patients with probable Alzheimer's disease (AD) over the course of 52 weeks of treatment with memantine or placebo. This was a multi-national, randomized, double-blind, placebo-controlled, fixed-dose 1-year study. Patients were randomized (1 : 1) to treatment with placebo or memantine. Patients randomized to memantine were up-titrated to the target dose of 20 mg/day over 4 weeks. MRI scans were collected at screening and at Weeks 4, 42, and 52. Secondary efficacy assessments included several cognitive and behavioral scales. 518 patients were screened, 278 patients were randomized, and 217 patients completed the study. In the primary efficacy analysis, the differences in TBA rates between memantine (15.2 mL/year) and placebo (15.3 mL/year) were not statistically significant (-0.04 mL/year [(95% CI: -2.60, 2.52), p = 0.98]). There was a statistically significant correlation between change in TBA and change in most cognitive and behavioral scale scores. Patients who were not treated with acetyl cholinesterase inhibitors (AChEIs) showed a significantly lower TBA rate than patients treated with AChEIs. Memantine had a placebo-level incidence of adverse events. There were no statistically significant differences between memantine and placebo in total brain or hippocampal atrophy rates in patients with probable AD treated for 1 year. The biological relevance of cerebral atrophy was supported by a significant correlation between rate of atrophy and decline in cognitive and behavioral outcomes.
The easier, the better: age, creatinine, ejection fraction score for operative mortality risk stratification in a series of 29,659 patients undergoing elective cardiac surgery.

Age, preoperative creatinine value, and ejection fraction are easily arranged in the age, creatinine, ejection fraction score to predict operative mortality in elective cardiac operations, as recently shown. We validate the age, creatinine, ejection fraction score in a large multicentric study.



We analyzed 29,659 consecutive patients who underwent elective cardiac operations in 14 Italian institutions during the period from 2004 to 2009. The operative (30-day) mortality rate was recorded for the entire population and for subgroups of patients based on the risk distribution. The predicted mortality was assessed using the additive and logistic European System for Cardiac Operative Risk Evaluations, and the age, creatinine, ejection fraction score. Accuracy and clinical performance of the different models were tested.



The observed mortality rate was 2.77% (95% confidence interval, 2.59-2.96). The predicted mortality rate was 2.84% (95% confidence interval, 2.79-2.88) for the age, creatinine, ejection fraction score (not significantly different from the observed rate), 6.26% for the additive European System for Cardiac Operative Risk Evaluation, and 9.67% for the logistic European System for Cardiac Operative Risk Evaluation (both significantly overestimated). For all deciles of risk distribution, the European System for Cardiac Operative Risk Evaluation significantly overestimated mortality risk; the age, creatinine, ejection fraction score slightly overestimated the mortality risk in very low-risk patients and significantly underestimated the mortality risk in very high-risk patients, correctly estimating the risk in 7 of 10 deciles. The accuracy of the age, creatinine, ejection fraction score was acceptable (area under the curve of 0.702). In a separate analysis, this value increased to 0.74 by excluding centers that reported no operative mortality. These values were similar or worse for the European System for Cardiac Operative Risk Evaluation.



The age, creatinine, ejection fraction score provides an accuracy level comparable to that of the European System for Cardiac Operative Risk Evaluation, with far superior clinical performance.