bluuebunny/crossref_metadata_2025_split huggingface dataset:
Midazolam microdose to determine systemic and pre‐systemic metabolic CYP3A activity in humans
Authors: Hohmann Nicolas , Kocheise Franziska , Carls Alexandra , Burhenne Jürgen , Haefeli Walter E. , Mikus Gerd 
Published: September 2014

AimWe aimed to establish a method to assess systemic and pre‐systemic cytochrome P450 (CYP) 3A activity using ineffective microgram doses of midazolam.MethodsIn an open, one sequence, crossover study, 16 healthy participants received intravenous and oral midazolam at microgram (0.001 mg intravenous and 0.003 mg oral) and regular milligram (1 mg intravenous and 3 mg oral) doses to assess the linearity of plasma and urine pharmacokinetics.ResultsDose‐normalized AUC and Cmax were 37.1 ng ml−1 h [95% CI 35.5, 40.6] and 39.1 ng ml−1 [95% CI 30.4, 50.2] for the microdose and 39.0 ng ml−1 h [95% CI 36.1, 42.1] and 37.1 ng ml−1 [95% CI 26.9, 51.3] for the milligram dose. CLmet was 253 ml min−1 [95% CI 201, 318] vs. 278 ml min−1 [95% CI 248, 311] for intravenous doses and 1880 ml min−1 [95% CI 1590, 2230] vs. 2050 ml min−1 [95% CI 1720, 2450] for oral doses. Oral bioavailability of a midazolam microdose was 23.4% [95% CI 20.0, 27.3] vs. 20.9% [95% CI 17.1, 25.5] after the regular dose. Hepatic and gut extraction ratios for microgram doses were 0.44 [95% CI 0.39, 0.49] and 0.53 [95% CI 0.45, 0.63] and compared well with those for milligram doses (0.43 [95% CI 0.37, 0.49] and 0.61 [95% CI 0.53, 0.70]).ConclusionThe pharmacokinetics of an intravenous midazolam microdose is linear to the applied regular doses and can be used to assess safely systemic CYP3A activity and, in combination with oral microdoses, pre‐systemic CYP3A activity.
Vaginal Birth After Cesarean in German Out‐of‐Hospital Settings: Maternal and Neonatal Outcomes of Women With Their Second Child
Authors: Beckmann Lea , Barger Mary , Dorin Lena , Metzing Sabine , Hellmers Claudia 
Published: September 2014

AbstractBackgroundTo offer vaginal birth after cesarean (VBAC) in a hospital setting is recommended in international guidelines, but offering VBAC in out‐of‐hospital settings is considered controversial. This study describes neonatal and maternal outcomes in mothers who started labor in German out‐of‐hospital settings.MethodIn a retrospective analysis of German out‐of‐hospital data from 2005 to 2011, included were 24,545 parae II with a singleton pregnancy in a cephalic presentation at term (1,927 with a prior cesarean and 22,618 with a prior vaginal birth).ResultThe overall VBAC rate was 77.8 percent. The intrapartum transfer rate to hospital was 38.3 percent (prior cesarean) versus 4.6 percent (prior vaginal) (p < 0.05), and the 10‐minute Apgar < 7 rate was 0.6 versus 0.2 percent (p < 0.05), and the nonemergency intrapartum transfer rate was 91.5 versus 85.0 percent (p < 0.05). Prolonged first stage of labor was the most common reason for intrapartum transfer in both groups. The leading reason for postpartum transfer was retained placenta.DiscussionThere was a high rate of successful VBAC in this study. The high nonemergency transfer rate for women with VBAC might mean that midwives are more cautious when attending women with a prior cesarean in out‐of‐hospital settings. Further studies are necessary to evaluate which women are suitable for VBAC in out‐of‐hospital settings.
Prognostic biomarkers in patients with localized natural killer/T‐cell lymphoma treated with concurrent chemoradiotherapy
Authors: Yamaguchi Motoko , Takata Katsuyoshi , Yoshino Tadashi , Ishizuka Naoki , Oguchi Masahiko , Kobayashi Yukio , Isobe Yasushi , Ishizawa Kenichi , Kubota Nobuko , Itoh Kuniaki , Usui Noriko , Miyazaki Kana , Wasada Izumi , Nakamura Shigeo , Matsuno Yoshihiro , Oshimi Kazuo , Kinoshita Tomohiro , Tsukasaki Kunihiro , Tobinai Kensei 
Published: September 2014

Concurrent chemoradiotherapy has become one of the standard management approaches for newly diagnosed localized nasal natural killer (NK)/T‐cell lymphoma (NKTCL). Few data are available on the prognostic biomarkers of NKTCL among patients treated with concurrent chemoradiotherapy. To evaluate the prognostic significance of immunophenotypic biomarkers for patients treated with concurrent chemoradiotherapy, latent membrane protein 1 (LMP1), cutaneous lymphocyte antigen (CLA) and cell origin were examined in samples from 32 patients who were enrolled in the Japan Clinical Oncology Group 0211 trial and treated with concurrent chemoradiotherapy. LMP1 and CLA were positive in 66% (19/29) and 29% (9/31) of the cases examined, respectively. The median follow‐up duration was 68 months (range, 61–94). The patients with LMP1‐positive tumors showed a better overall survival (OS) than the patients with LMP1‐negative tumors (hazard ratio, 0.240; 95% confidence interval [CI], 0.057–1.013; 80% CI, 0.093–0.615; P = 0.035). All five patients with LMP1‐negative tumors who experienced disease progression died of lymphoma, and both patients with local failure had LMP1‐negative tumors. There was no significant difference in OS according to CLA expression. A total of 27 (84%) cases were of NK‐cell origin, two were of αβ T‐cell origin and three were of γδ T‐cell origin. In contrast to those with tumors of NK‐cell origin, all five patients with NKTCL of T‐cell origin were alive without relapse at the last follow up. Our results indicate that LMP1 expression is a favorable prognostic marker and suggest that a T‐cell origin of the tumor may be a favorable prognostic marker for patients with localized NKTCL treated with concurrent chemoradiotherapy.
Duration of day care attendance during infancy predicts asthma at the age of seven: the Cincinnati Childhood Allergy and Air Pollution Study
Authors: Cheng G. , Smith A. M. , Levin L. , Epstein T. , Ryan P. H. , LeMasters G. K. , Khurana Hershey G. K. , Reponen T. , Villareal M. , Lockey J. , Bernstein D. I. 
Published: September 2014

SummaryBackgroundStudies vary with respect to the reported effects of day care attendance on childhood asthma.ObjectivesTo evaluate the independent and combined effects of day care attendance and respiratory infections on the development of asthma at the age of seven in a prospective birth cohort.MethodAt the age of seven, the study sample included 589 children with complete data of 762 enrolled at birth. Day care hours and number of respiratory infections were reported in follow‐up questionnaires through age four. At 7 years of age, asthma was diagnosed in 95 children (16%), based on predefined symptoms criteria confirmed by either asthma FEV1 reversibility after bronchodilator or a positive methacholine test (PC20 ≤ 4 mg/mL). Logistic regression was used to investigate the relationships between asthma at the age of seven, cumulative hours of day care attendance and reported respiratory infections at ages 1–4.ResultsIn the univariate analyses, day care attendance at 12 months was associated with an increased risk of asthma [odds ratio (OR) = 1.8, 95% confidence interval (CI) = 1.1–3.0]. Both upper and lower respiratory infections at 12 months also increased the likelihood of asthma [OR = 2.4 (1.4–4.1); OR = 2.3 (1.5–3.7), respectively]. In the final multivariate logistic model, cumulative hours of day care attendance and number of lower respiratory infections at 12 months were associated with asthma [OR = 1.2 (1.1–1.5); OR = 1.4 (1.2–1.7), respectively]. However, a threshold of greater than 37.5 hours per week of day care attendance was associated with a lower risk of asthma [OR = 0.6 (0.4–0.9)].ConclusionDepending on duration of attendance, day care during infancy can either increase or reduce risk of asthma at the age of seven.
Zebrafish as a systems toxicology model for developmental neurotoxicity testing
Authors: Nishimura Yuhei , Murakami Soichiro , Ashikawa Yoshifumi , Sasagawa Shota , Umemoto Noriko , Shimada Yasuhito , Tanaka Toshio 
Published: September 2014

AbstractThe developing brain is extremely sensitive to many chemicals. Exposure to neurotoxicants during development has been implicated in various neuropsychiatric and neurological disorders, including autism spectrum disorder, attention deficit hyperactive disorder, schizophrenia, Parkinson's disease, and Alzheimer's disease. Although rodents have been widely used for developmental neurotoxicity testing, experiments using large numbers of rodents are time‐consuming, expensive, and raise ethical concerns. Using alternative non‐mammalian animal models may relieve some of these pressures by allowing testing of large numbers of subjects while reducing expenses and minimizing the use of mammalian subjects. In this review, we discuss some of the advantages of using zebrafish in developmental neurotoxicity testing, focusing on central nervous system development, neurobehavior, toxicokinetics, and toxicodynamics in this species. We also describe some important examples of developmental neurotoxicity testing using zebrafish combined with gene expression profiling, neuroimaging, or neurobehavioral assessment. Zebrafish may be a systems toxicology model that has the potential to reveal the pathways of developmental neurotoxicity and to provide a sound basis for human risk assessments.
Long‐Term Bone Stability around 312 Rough‐Surfaced Immediately Placed Implants with 2–12‐Year Follow‐Up
Authors: Wagenberg Barry , Froum Stuart J. 
Published: September 2014

AbstractPurposeThe purpose of this study was to retrospectively evaluate bone stability around implants with anodic oxidized surfaces and correlate this with variables compared in a previous study.Materials and MethodsA total of 312 implants with anodic oxidized surfaces were separated from a pool of 1,187 implants placed immediately following tooth extraction. Radiographs made at the time of implant placement were compared to radiographs taken at 2–12 years' follow‐up. An independent radiologist used the known distance (mm) between peaks of adjacent threads to calculate actual bone loss measurements. Measurements were evaluated by thread of bone fill on both the mesial and distal of each implant. If <50% of the thread had bone fill, the entire thread was assumed devoid of bone. All 312 implants were measured and a Mann–Whitney rank‐sum test performed to test the significance of differences in mean bone loss relative to the factors studied.ResultsThe overall mean bone loss of the 312 implants was 0.4 mm (± 0. 80 mm) over a 2–12‐year follow‐up period with a mean duration of 7.4 years. Bone measurements in 95.5% of the implants were performed 6 years or more post‐placement. Bone loss of <1.5 mm was found in 92% of implants. No statistically significant differences were seen in mean bone loss by gender, smokers versus non‐smokers, tooth position (except for molars), or immediately loaded or immediate tooth replacement versus two‐stage implants. Parameters that demonstrated statistically significant differences were splinted versus non‐splinted implants, molars in maxilla versus mandible, regular (3.75–4.0 mm diameter) versus wide (5.0–6.0 mm diameter) platforms, and anodic oxidized surfaces versus other implant surfaces studied.ConclusionsThe mesial–distal bone loss of anodic oxidized surface (TiUnite) implants over a 2–12‐year period (mean 7.4 years) was significantly less compared with machined implants placed with the same immediate implant placement protocol (0.4 mm vs 0.6 mm). Although several variables showed statistically significant differences in bone loss, the clinical significance could be questioned, as the maximum mean bone loss was 0.3 mm or less when comparing the various factors. The procedures used to place the implant and the strict maintenance protocol appear to be important aspects of the overall long‐term success reported in this study in terms of measuring marginal bone loss around immediately placed implants.
To Sleep or Not to Sleep: A Repeated Daily Challenge for African American Children
Authors: Spruyt Karen , Alaribe Calista U. , Nwabara Odochi U. 
Published: September 2014

SummaryAimsSleep is important for children, because of the impact on their development and well‐being. Previous survey research suggested that poor sleep occurs more frequently in minorities. However, objective data characterizing their sleep patterns are lacking.MethodsChildren enrolled in a 1‐year cross‐sectional sequence designed study centered on a 14‐day objective sleep recording, which was repeated three times. Children lived on the South Side of Chicago and were self‐defined as being African Americans.ResultsFindings reflect data of 24 children with a mean age of 5.4 ± 1.7 years of which 54.2% were girls. They slept at night 6.51 h and during the day changeably 1.42 h, likely being noon naps during the week and afternoon naps on Saturday and Sunday. Variability in quality of sleep, and also nighttime sleep duration, especially on Friday and Saturday, was characteristic. The highest variability was noted in sleep onset and offset latency, and in the quality of napping. The interrelation of daytime and nighttime sleep changes was suggestive of “catch‐up” daytime sleep.ConclusionAt nighttime children habitually obtained few hours of sleep with diurnal sleep fluctuations likely being “a need” and “a chance.” Interventions might emphasize on creating optimal opportunities to sleep.
Causes and Consequences of Gray Matter Heterotopia
Authors: Watrin Françoise , Manent Jean‐Bernard , Cardoso Carlos , Represa Alfonso 
Published: September 2014

SummaryThe objective of this article is to review the pathophysiological bases of gray matter heterotopia and to appreciate their involvement in brain cortical development and functional consequences, namely epilepsy. The development of the cerebral cortex results from complex sequential processes including cell proliferation, cell migration, cortical organization, and formation of neuronal networks. Disruption of these steps yields different types of cortical malformations including gray matter heterotopia, characterized by the ectopic position of neurons along the ventricular walls or in the deep white matter. Cortical malformations are major causes of epilepsy, being responsible for up to 40% of drug‐resistant epilepsy, and the cognitive level of affected patients varies from normal to severely impaired. This review reports data from human patients and animal models highlighting the genetic causes for these disorders affecting not only neuronal migration but also the proliferation of cortical progenitors. Therefore, gray matter heterotopias should not be considered as solely due to an abnormal neuronal migration and classifying them as such may be too restrictive. The review will also summarize literature data indicating that besides ectopic neurons, neighbor cortical areas also play a consistent role in epileptogenesis, supporting the notion that plastic changes secondary to the initial malformation are instrumental in the pathophysiology of epilepsy in affected patients.
Double‐balloon endoscopy is safe and effective for the diagnosis and treatment of small‐bowel disorders: Prospective multicenter study carried out by expert and non‐expert endoscopists in Japan
Authors: Yamamoto Hironori , Yano Tomonori , Ohmiya Naoki , Tanaka Shu , Tanaka Shinji , Endo Yutaka , Matsuda Tomoki , Matsui Toshiyuki , Iida Mitsuo , Sugano Kentaro 
Published: September 2014

Background and AimDouble‐balloon endoscopy (DBE) has enabled direct, detailed examination of the entire small bowel with interventional capabilities. Although its usefulness is recognized, efficacy and safety have not been extensively evaluated by prospective multicenter studies. To evaluate the efficacy and safety of DBE carried out by expert and non‐expert endoscopists, a prospective, multicenter study was conducted in five university hospitals and a general hospital in Japan.MethodsA total of 120 patients who underwent 179 procedures were enrolled in the study. Experts carried out 129 procedures and non‐experts carried out 50 procedures. Primary and secondary end points were evaluation of safety, the rate of achievement of procedural objectives, namely, identification of a new lesion, detailed examination to establish a therapeutic strategy, or exclusion of significant lesions by total enteroscopy, and rate of successful examination of the entire small bowel and evaluation of safety.ResultsOverall rate of achievement of procedural objectives was 82.5% (99/120). Overall success rate for examination of the entire small bowel was 70.8% (34/48). Incidence of adverse events was 1.1% (a mucosal injury and an episode of pyrexia in two of 179 examinations). No severe adverse events were encountered. There were no significant differences in any of the outcome measures comparing expert and non‐expert operators.ConclusionsDBE is effective and safe for patients with suspected small bowel diseases, and can be safely carried out even by a non‐expert under the supervision of an expert, following a simple training program.
Language dominance assessment in a bilingual population: Validity of fMRI in the second language
Authors: Centeno Maria , Koepp Matthias J. , Vollmar Christian , Stretton Jason , Sidhu Meneka , Michallef Caroline , Symms Mark R. , Thompson Pamela J. , Duncan John S. 
Published: September 2014

SummaryObjectiveAssessment of language dominance using functional magnetic resonance imaging (fMRI) is a standard tool to estimate the risk of language function decline after epilepsy surgery. Although there has been considerable research in the characterization of language networks in bilingual individuals; little is known about the clinical usefulness of language mapping in a secondary language in patients with epilepsy, and how language lateralization assessed by fMRI may differ by the use of native or a secondary language paradigms. In this study we investigate language representation in a population of nonnative English speakers to assess differences in fMRI language lateralization between the first (native) and second language (English).MethodsSixteen nonnative English‐speaking patients with focal drug‐resistant epilepsy underwent language fMRI in their first (native) language (L1) and in English (L2). Differences between language maps using L1 and L2 paradigms were examined at the single subject level by comparing within‐subject lateralization indexes obtained for each language. Differences at the group level were examined for each of the tasks and languages.ResultsGroup maps for the second language (English) showed overlapping areas of activation with the native language, but with larger clusters, and more bilaterally distributed than for the first language. However, at the individual level, lateralization indexes were concordant between the two languages, except for one patient with bilateral hippocampal sclerosis who was left dominant in English and showed bilateral dominance for verb generation and right dominance for verbal fluency in his native tongue.SignificanceLanguage lateralization can generally be reliably derived from fMRI tasks in a second language provided that the subject can follow the task. Subjects with greater likelihood of atypical language representation should be evaluated more carefully, using more than one language paradigm.
Engineering microorganisms based on molecular evolutionary analysis: a succinate production case study
Authors: Ma Xianghui , Zhang Xinbo , Wang Baiyun , Mao Yufeng , Wang Zhiwen , Chen Tao , Zhao Xueming 
Published: September 2014

AbstractEvolution has resulted in thousands of species possessing similar metabolic enzymes with identical functions that are, however, regulated by different mechanisms. It is thus difficult to select optimal gene to engineer novel or manipulated metabolic pathways. Here, we tested the ability of molecular evolutionary analysis to identify appropriate genes from various species. We calculated the fraction of synonymous substitution and the effective number of codons (ENC) for nine genes stemming from glycolysis. Our research indicated that an enzyme gene with a stronger selective constraint in synonymous sites would mainly regulate corresponding reaction flux through altering the concentration of the protein, whereas those with a more relaxed selective constraint would primarily affect corresponding reaction flux by changing kinetic properties of the enzyme. Further, molecular evolutionary analysis was investigated for three types of genes involved in succinate precursor supply by catalysis of pyruvate. In this model, overexpression of Corynebacterium glutamicum pyc should result in greater conversion of pyruvate. Succinate yields in two Escherichia coli strains that overexpressed each of the three types of genes supported the molecular evolutionary analysis. This approach may thus provide an alternative strategy for selecting genes from different species for metabolic engineering and synthetic biology.
Cell elasticity is an important indicator of the metastatic phenotype of melanoma cells
Authors: Sarna Michal , Zadlo Andrzej , Hermanowicz Pawel , Madeja Zbigniew , Burda Kvetoslava , Sarna Tadeusz 
Published: September 2014

AbstractThe relationship between melanin pigmentation and metastatic phenotype of melanoma cells is an intricate issue, which needs to be unambiguously determined to fully understand the process of metastasis of malignant melanoma. Despite significant research efforts undertaken to solve this problem, the outcomes are far from being satisfying. Importantly, none of the proposed explanations takes into consideration biophysical aspects of the phenomenon such as cell elasticity. Recently, we have demonstrated that melanin granules dramatically modify elastic properties of pigmented melanoma cells. This prompted us to examine the mechanical effects of melanosomes on the transmigration abilities of melanoma cells. Here, we show for the first time that melanin granules inhibit transmigration abilities of melanoma cells in a number of granules dependent manner. Moreover, we demonstrate that the inhibitory effect of melanosomes is mechanical in nature. Results obtained in this study demonstrate that cell elasticity may play a key role in the efficiency of melanoma cells spread in vivo. Our findings may also contribute to better understanding of the process of metastasis of malignant melanoma.
Compound K inhibits MMP‐1 expression through suppression of c‐Src‐dependent ERK activation in TNF‐α‐stimulated dermal fibroblast
Authors: Lee Chang Seok , Bae Il‐Hong , Han Jiwon , Choi Gye‐young , Hwang Kyung‐Hwan , Kim Dong‐Hyun , Yeom Myeong‐Hun , Park Young‐Ho , Park Miyoung 
Published: September 2014

AbstractCompound K (CK) is one of the major metabolites of ginsenosides exhibiting a variety of pharmacological properties such as anti‐ageing, anti‐oxidation and anti‐inflammatory activities. However, the protective efficacy of CK in abnormal skin conditions with inflammatory responses was not examined. Here, we investigated the effects of CK on matrix metalloproteinase‐1 (MMP‐1) and type I procollagen production in tumor necrosis factor‐α (TNF‐α)‐stimulated human skin fibroblasts HS68 cells and human skin equivalents. We found that CK suppressed MMP‐1 secretion and increased the level of reduced type I procollagen secretion, caused by the inhibition of extracellular signal‐regulated kinase (ERK) activation, but not p38 and c‐Jun N‐terminal kinase (JNK) activation in TNF‐α‐stimulated HS68 cells. Then, we focused on the involvement of the c‐Src and epidermal growth factor receptor (EGFR) as upstream signalling molecules for ERK activation by TNF‐α in HS68 cells. CK suppressed the phosphorylation of c‐Src/EGFR by TNF‐α, which led to the inactivation of downstream signalling molecules including AKT and MEK. In addition, CK suppressed AP‐1 (c‐jun and c‐fos) phosphorylation as downstream transcription factors of active ERK for MMP‐1 expression in TNFα‐stimulated HS68 cells. These results showed novel mechanisms by which CK inhibits TNF‐α‐induced MMP‐1 expression through the inactivation of c‐Src/EGFR‐dependent ERK/AP‐1 signalling pathway, resulting in the inhibition of collagen degradation in human fibroblast cells. Therefore, CK may be a promising protective agent for the treatment of inflammatory skin conditions such as skin ageing and atopic dermatitis.