bluuebunny/crossref_metadata_2025_split huggingface dataset:
First pass intestinal and liver metabolism of paracetamol in a microfluidic platform coupled with a mathematical modeling as a means of evaluating ADME processes in humans
Authors: Prot Jean Matthieu , Maciel Luis , Bricks Thibault , Merlier Franck , Cotton Jérôme , Paullier Patrick , Bois Fréderic Yves , Leclerc Eric 
Published: June 2014

ABSTRACTWe developed a microfluidic platform to investigate paracetamol intestinal and liver first pass metabolism. This approach was coupled with a mathematical model to estimate intrinsic in vitro parameters and to predict in vivo processes. The kinetic modeling estimated the paracetamol and paracetamol sulfate permeabilities, the sulfate and glucuronide effluxes in the intestine compartment. Based on a gut model, we estimated intrinsic intestinal clearance of between 26 and 77 L/h for paracetamol in humans, a permeability of 10 L/h, and a gut availability between 0.17 and 0.53 (compared to 0.95—1 in vivo). The role played by the liver in paracetamol metabolism was estimated via in vitro intrinsic clearances of 7.6, 13.6, and 11.5 µL/min/106 cells for HepG2/C3a, rat primary hepatocytes, and human primary hepatocytes, respectively. Based on a parallel tube model to describe the liver, the paracetamol hepatic clearance, and the paracetamol hepatic availability in humans were estimated at 6.5 mL/min/kg of bodyweight (BDW) and 0.7, respectively (when compared to 5 mL/min/kg of BDW and 0.77 to 0.88 for in vivo values, respectively). The drug availability was predicted ranging between 0.24 and 0.41 (0.88 in vivo). The overall approach provided a first step in an integrated strategy combining in silico/in vitro methods based on microfluidic for evaluating drug absorption, distribution and metabolism processes. Biotechnol. Bioeng. 2014;111: 2027–2040. © 2014 Wiley Periodicals, Inc.
Advances in diagnostic modalities to detect occult lymph node metastases in head and neck squamous cell carcinoma
Authors: de Bree Remco , Takes Robert P. , Castelijns Jonas A. , Medina Jesus E. , Stoeckli Sandro J. , Mancuso Anthony A. , Hunt Jennifer L. , Rodrigo Juan P. , Triantafyllou Asterios , Teymoortash Afshin , Civantos Francisco J. , Rinaldo Alessandra , Pitman Karen T. , Hamoir Marc , Robbins K. Thomas , Silver Carl E. , Hoekstra Otto S. , Ferlito Alfio 
Published: June 2014

AbstractRegional metastasis is a prominent feature of head and neck squamous cell carcinoma (HNSCC) and is an important prognostic factor. The currently available imaging techniques for assessment of the neck have limitations in accuracy; thus, elective neck dissection has remained the usual choice of management of the clinically N0 neck (cN0) for tumors with significant (≥20%) incidence of occult regional metastasis. As a consequence, the majority of patients without regional metastasis will undergo unnecessary treatment. The purpose of this review was to discuss new developments in techniques that potentially improve the accuracy of the assessment of the neck in patients with HNSCC. Although imaging has improved in the last decades, a limitation common to all imaging techniques is a lack of sensitivity for small tumor deposits. Therefore, complementary to improvements in imaging techniques, developments in more invasive diagnostic procedures, such as sentinel node biopsy (SNB) will add to the accuracy of diagnostic algorithms for the staging of the neck. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1829–1839, 2015
Hemocompatibility and cytocompatibility of the hirudin‐modified silk fibroin
Authors: Sun Dan , Hao Yunxia , Yang Gaoqiang , Wang Jiannan 
Published: June 2014

AbstractHirudin (Hir), a thrombin direct inhibitor, was used to modify a polyethylene glycol diglycidyl ether (PEG‐DE) crosslinked regenerated silk fibroin (SF) material to improve hemocompatibility. Hemolysis characteristics, platelet adhesion, platelet activity, and plasma recalcification time were investigated using absorption spectrometry, scanning electron microscopy, MTT analysis, and the time counting method. Hirudin could be grafted evenly to the silk fibroin, and the modified material was resistant to hemolysis at ratios of less than 0.5%. Scanning electron microscopy and MTT results showed that platelet adhesion and aggregation activity decreased after modificaton with trace amounts of hirudin, compared with PEG‐DE crosslinked and ethanol‐treated silk fibroin film. Plasma recalcification of PEG‐DE crosslinked silk fibroin film was slower than with ethanol‐treated material, and this increased slightly after hirudin modification. Furthermore, L929, HAVSMC, and HUVEC cells adhered to the modified material, grew well, and possessed high proliferation activity on SF/Hir blend films. This study suggests that hirudin could improve the anticoagulation properties of regenerated silk fibroin materials. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 556–562, 2015.
“¡Fantástico!”
Authors: DeNicolo Christina P. 
Published: June 2014

AbstractDrawing from a qualitative case study that examined the language practices and learning in a first grade bilingual classroom, the author discusses one teacher's daily process for the literacy event of the morning message. Primary findings indicate that the ways the teacher listened and responded to students during the morning message provided validation regarding their knowledge and role in the classroom. Several forms of validation were identified such as: stating agreement with students’ thoughts and opinions, identification of students’ intellectual strategies, and recognition of their cultural and linguistic knowledge. The forms of validation used during morning message supported student learning of academic language across their developing languages of Spanish and English as well as their ability to see themselves as valuable members of the learning community. This study builds on literacy research by exploring how morning message can promote student engagement, literacy development and metalinguistic awareness.
Biodiesel Synthesis in a Solvent‐Free System by Recombinant Rhizopus oryzae Lipase. Study of the Catalytic Reaction Progress
Authors: Canet Albert , Dolors Benaiges M. , Valero Francisco 
Published: June 2014

AbstractThe recombinant 1,3‐positional selective Rhizopus oryzae lipase (rROL) was used to synthesize biodiesel and monoacylglycerols simultaneously. The reaction was carried out in a solvent‐free system with the enzyme immobilized on octadecyl‐Sepabeads. Using response surface methodology, the methyl ester yield was optimized by means of the study of the effect of water, substrate molar ratio (methanol:olive oil) and methanol stepwise addition. It was concluded that in order to prevent enzyme inactivation by methanol, alcohol should be added slowly; otherwise a large amount of water would be present. Taking the best conditions, a 50.3 % yield was achieved in 3 h, which corresponds to 75.4 % of the acyl groups at the 1,3‐position undergoing transesterification. It was also concluded that methyl esters result from the esterification of the free fatty acid hydrolyzed by the enzyme and also from a direct transesterification of oil. In addition, the fatty acid selectivity of rROL was found not to favor one fatty acid in olive oil over another.
The (late?) modern family: The family's significance for adolescents in Germany and Israel
Authors: Girsh Yaron 
Published: June 2014

ABSTRACTThis study presents German and Israeli youth's heroes and role models. Two hundred twenty‐six students from 22 high schools took part in small group interviews. Despite differences in the normative place of the family in the two cultures, the comparison reveals significant similarities between their views and what attributes the subjects assign to their families. Three main models of family members as hero arise from the data: The Self‐made Person; sacrifice and pro‐social action; and contending with everyday reality. The results point to a) the fading of traditional heroes from the imagination of youth in post‐industrial societies; b) the substantive place the family holds in young people's lives. I suggest that the rise of uncertainty and risk in the current socio‐historical constellation, contributes to adolescents' choice of figures from their immediate environments that embody safety and a moral framework.
Endogenous XIAP, but not other members of the inhibitory apoptosis protein family modulates cerebellar granule neurons survival
Authors: Blancas Sugela , Fadó Rut , Rodriguez‐Alvarez José , Morán Julio 
Published: June 2014

AbstractProgrammed cell death plays a critical role during cerebellar development. In particular, it has been shown in vivo and in vitro that developing cerebellar granule neurons (CGN) die apoptotically. Apoptosis involves a series of morphological changes and the activation of caspases. Inhibitor of apoptosis proteins (IAPs) is implicated in negative regulation of caspase activation and apoptotic cell death. Although apoptotic death of CGN has been extensively studied, there is no information about the role of IAPs in the developing cerebellum. Here, we studied the participation of some members of IAPs in the survival of the developing rat CGN in culture and under physiological conditions. Under these conditions, we found a differential expression pattern of cIAP‐1, cIAP‐2, XIAP and survivin during cerebellar development in an age‐dependent manner, highlighting the significant increase of XIAP levels. We also detected an interaction between XIAP and caspase 3 at postnatal day (P) 12 and 16. On the other hand, we found a significant decrease of XIAP levels in cultured CGN maintained in chronic potassium deprivation, an apoptotic condition, suggesting a possible relationship between XIAP levels and neuronal viability. Under these conditions, we also detected the interaction of XIAP with active caspase‐3. The down‐regulation of XIAP in CGN cultured under survival conditions (chronic potassium depolarization) induced a reduction of cell viability and an increment of apoptotic cells. These findings support the idea that IAPs could be involved in the survival of CGN and that XIAP might be critical for neuronal survival in cerebellar development and during chronic depolarization in cultured CGN through a mechanism involving caspase inhibition.
Proprioceptive-induced seizure in diabetic non-ketotic state: A video case report
Authors: Meenakshi-Sundaram Salvadeeswaran , Nagendran Karthik Somalinga , Swaminathan Krishnan , Rajavel Thembavani , Dharmapillai Amala , Sundar Bharathi 
Published: June 2014

AbstractA 63-year-old diabetic gentleman with proprioceptive-induced seizures is reported. Marked hyperglycemia due to discontinuation of anti-diabetic medication was the precipitating cause. Distinctive clinical feature of this case was recurrent focal motor seizures involving the left upper limb precipitated by volitional movements of the same limb and self-aborted by holding the affected limb with the contralateral limb. This was accompanied by left brachial weakness without corresponding lesions on cranial MRI. Despite rapid achievement of euglycemia, seizures persisted and required anticonvulsant polytherapy for effective control.
The role of advocacy in the national strategy for maternal death review in Nigeria
Authors: Achem Fred F. , Agboghoroma Chris O. , Adeoye Moses O. 
Published: June 2014

AbstractStrategic advocacy has played a substantial role in the development and implementation of maternal death review (MDR) in Nigeria. Stakeholders that include the Society of Gynaecology and Obstetrics of Nigeria have partnered with the Federal Ministry of Health to ensure a robust arrangement that will guarantee the success of MDR in this country. Consequently, it is envisaged that the program will both contribute to a sustainable reduction in the maternal mortality ratio and promote improvements in maternal health care. The Nigerian experience indicates that the influence of stakeholders, such as professional organizations, is essential to drive the development of MDR programs through provision of advocacy and technical support. The current convergence of factors—including global support, political will, technical innovations, and increased financial resources—provides an ideal opportunity to make MDR a reality for all countries.
Incidence of ambulatory care visits after needlestick and sharps injuries among healthcare workers in Taiwan: A nationwide population‐based study
Authors: Wang Shyang‐Guang , Hung Chin‐Tun , Li Shu‐Fen , Lu Yu‐Chun , Chang Shu‐Chuan , Lee Horng‐Mo , Pai Lee‐Wen , Lai Fu‐I , Huang Yu‐Wen , Chung Yueh‐Chin 
Published: June 2014

AbstractHealthcare professionals have a high risk of needlestick and sharps injuries (NSIs), which have a high potential for disease transmission. Ambulatory care follow up is essential, but is usually overlooked. This study aimed to investigate the annual and cumulative (age‐, sex‐, and subtype‐specific) incidences of ambulatory care visits after NSIs. This study was also designed to evaluate the incidences of blood‐borne diseases associated with NSIs among Taiwanese health professionals in Taiwan between 2004 and 2010. Data were obtained from the National Health Insurance Research Database, which contains anonymized records representing approximately 99% of the Taiwan population. A total of 4443 nurse healthcare workers (NHCWs) and 3138 non‐nurse healthcare workers (NNHCWs), including physicians, medical technologists, and other health professionals were included in this longitudinal study. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The Mantel‐Haenszel method was used to adjust for sex, age, and type of affiliation. Results showed that the annual incidence of ambulatory care visits of NHCWs increased from 0.7% in 2004 to 1.9% in 2010; this incidence was significantly higher than that of NNHCWs (from 0.3% in 2004 to 0.5% in 2010) in any yearly comparison (p < 0.05). The sex‐adjusted 7‐year cumulative incidence rate was 3.23 (95% CI = 1.23–8.45) in males and 3.92 (95% CI = 2.70–5.69) in females (p < 0.05). The age‐adjusted 7‐year cumulative incidence rate was 2.74 (95% CI = 1.99–3.77) and 2.14 (95% CI = 1.49–3.07) in subjects ≤ 30 and ≥31 years old, respectively (p < 0.0005). The affiliation‐adjusted 7‐year cumulative incidence rate was 1.89 (95% CI = 1.21–2.94) in medical centers and 3.33 (95% CI = 2.51–4.41) in nonmedical centers (p < 0.01). In conclusion, NSIs increased steadily from 2004 to 2010 in Taiwan with NHCWs having higher NSIs incidences than NNHCWs. A routine ambulatory care visit after NSIs can prevent blood‐borne transmission, especially for NHCWs. Educational programs may be helpful for reducing the incidence of NSIs and increasing ambulatory care visit ratios after NSIs.
EARLY BUD-BREAK 1 (EBB1) is a regulator of release from seasonal dormancy in poplar trees
Authors: Yordanov Yordan S. , Ma Cathleen , Strauss Steven H. , Busov Victor B. 
Published: June 2014

SignificanceTiming of vegetative bud dormancy is an environmentally and economically important trait whose importance will grow due to rapid climate changes. However, the underpinning regulatory mechanisms are still poorly understood. We report the identification and characterization of theEarly Bud-Break 1(EBB1) gene in poplar that regulates the timing of bud-break. EBB1 plays a major and integrative role in the reactivation of the shoot apical meristem after winter dormancy. The knowledge about EBB1 function can enable novel approaches for population management, molecular breeding, and genetic engineering of dormancy-associated traits.
BEETL-fastq: a searchable compressed archive for DNA reads
Authors: Janin Lilian , Schulz-Trieglaff Ole , Cox Anthony J. 
Published: June 2014

AbstractMotivation: FASTQ is a standard file format for DNA sequencing data, which stores both nucleotides and quality scores. A typical sequencing study can easily generate hundreds of gigabytes of FASTQ files, while public archives such as ENA and NCBI and large international collaborations such as the Cancer Genome Atlas can accumulate many terabytes of data in this format. Compression tools such as gzip are often used to reduce the storage burden but have the disadvantage that the data must be decompressed before they can be used.Here, we present BEETL-fastq, a tool that not only compresses FASTQ-formatted DNA reads more compactly than gzip but also permits rapid search for k -mer queries within the archived sequences. Importantly, the full FASTQ record of each matching read or read pair is returned, allowing the search results to be piped directly to any of the many standard tools that accept FASTQ data as input.Results: We show that 6.6 terabytes of human reads in FASTQ format can be transformed into 1.7 terabytes of indexed files, from where we can search for 1, 10, 100, 1000 and a million of 30-mers in 3, 8, 14, 45 and 567 s, respectively, plus 20 ms per output read. Useful applications of the search capability are highlighted, including the genotyping of structural variant breakpoints and ‘ in silico pull-down’ experiments in which only the reads that cover a region of interest are selectively extracted for the purposes of variant calling or visualization.Availability and implementation: BEETL-fastq is part of the BEETL library, available as a github repository at github.com/BEETL/BEETL.Contact: acox@illumina.com
European Society for Pediatric Gastroenterology, Hepatology, and Nutrition Syllabus for Subspecialty Training
Authors: D'Antiga Lorenzo , Nicastro Emanuele , Papadopoulou Alexandra , Mearin Maria L. , Tzivinikos Christos , Vandenplas Yvan , van Goudoever Hans , Baumann Ulrich , Troncone Riccardo , Koletzko Berthold 
Published: June 2014

ABSTRACTThe requirements for and conditions of subspecialty training in paediatric gastroenterology, hepatology, and nutrition (PGHN) are rather variable across European countries. The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) agreed on a training syllabus aimed to foster a harmonised European PGHN curriculum and to support national PGHN societies and governmental bodies to promote and establish high‐quality training programmes and levels of certification in the field. The document provides PGHN training prerequisites and objectives and the basic knowledge elements to acquire the clinical, technical, and management skills needed. Guidelines and instruments for self‐monitoring and appraisal are proposed, and a logbook is available online. These training standards are a first step towards a European certification and recognition as a specialist in PGHN.
Clinical Patterns and Outcome of Early‐Onset Inflammatory Bowel Disease
Authors: Ledder Oren , Catto‐Smith Anthony G. , Oliver Mark R. , Alex George , Cameron Donald J.S. , Hardikar Winita 
Published: June 2014

ABSTRACTWe sought to determine whether extremely‐early‐onset childhood inflammatory bowel disease (age <6 years; 20 ulcerative colitis [UC], 8 Crohn disease [CD], 2 indeterminate, sequentially diagnosed) was clinically more severe than in older children (6–17 years; 19 UC, 39 CD, 2 indeterminate). Early‐onset UC was marked by less abdominal pain at presentation, but an aggressive course with a significant reduction in weight‐for‐age, increased use of immunosuppressants, and more surgery. Children with early‐onset CD were more likely to have bloody stools at presentation and an isolated colitis. This study supports the suggestion that inflammatory bowel disease phenotype differs in early‐onset disease.
Liver Transplantation for Classical Maple Syrup Urine Disease
Authors: Díaz Victoria M. , Camarena Carmen , de la Vega Ángela , Martínez‐Pardo Mercedes , Díaz Carmen , López Manuel , Hernández Francisco , Andrés Ane , Jara Paloma 
Published: June 2014

ABSTRACTObjectives:The aim of the study was to evaluate indications, results, and clinical and neurological evolution in children who have undergone liver transplantation for classical maple syrup urine disease (MSUD).Methods:Descriptive study of liver transplantation for MSUD between 1991 and 2012. Eight patients were transplanted.Results:Indications for transplant were poor metabolic control expressed as significant psychomotor disabilities (4 had psychomotor delays, 5 had spasticity, and 5 had epilepsy) and poor quality of life (mean number of acute metabolic decompensations and mean number of total hospitalizations before transplantation 5 and 12, respectively). Four required nasogastric tube, with a maximum 4 g/day protein‐restricted diet in all of them. Seven sustained significant alterations in brain magnetic resonance imaging. Mean leucine and alloisoleucine levels were 608 (standard deviation [SD] 516) and 218 μmol/L (SD 216), respectively. All of the patients received transplants with deceased‐donor livers, with ages between 1.5 and 2.5 years (mean 1.78 years). Mean posttransplantation follow‐up period was 12.2 years (range 5–21 years). Final patient and graft survival was 87.5% and 75%, respectively. Following transplantation, none required hospitalization in the last 3 years nor did any have new acute metabolic decompensations following a normal diet. Five followed normal schooling, 2 had motor disabilities, and 2 had convulsive crises. Brain magnetic resonance imaging was taken in 4 patients, showing neuroimage improvement in 3 of them. Mean leucine levels were <350 μmol/L from the immediate posttransplantation period (mean 225 μmol/L, SD 78), with a maximum alloisoleucine level of 20 μmol/L.Conclusions:Liver transplantation is an effective treatment for classical MSUD that arrests brain damage, although it does not reverse the process.
COP1 and phyB Physically Interact with PIL1 to Regulate Its Stability and Photomorphogenic Development inArabidopsis
Authors: Luo Qian , Lian Hong-Li , He Sheng-Bo , Li Ling , Jia Kun-Peng , Yang Hong-Quan 
Published: June 2014

AbstractIn Arabidopsis thaliana, the cryptochrome and phytochrome photoreceptors act together to promote photomorphogenic development. The cryptochrome and phytochrome signaling mechanisms interact directly with CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1), a RING motif–containing E3 ligase that acts to negatively regulate photomorphogenesis. COP1 interacts with and ubiquitinates the transcription factors that promote photomorphogenesis, such as ELONGATED HYPOCOTYL5 and LONG HYPOCOTYL IN FAR-RED1 (HFR1), to inhibit photomorphogenic development. Here, we show that COP1 physically interacts with PIF3-LIKE1 (PIL1) and promotes PIL1 degradation via the 26S proteasome. We further demonstrate that phyB physically interacts with PIL1 and enhances PIL1 protein accumulation upon red light irradiation, probably through suppressing the COP1–PIL1 association. Biochemical and genetic studies indicate that PIL1 and HFR1 form heterodimers and promote photomorphogenesis cooperatively. Moreover, we demonstrate that PIL1 interacts with PIF1, 3, 4, and 5, resulting in the inhibition of the transcription of PIF direct-target genes. Our results reveal that PIL1 stability is regulated by phyB and COP1, likely through physical interactions, and that PIL1 coordinates with HFR1 to inhibit the transcriptional activity of PIFs, suggesting that PIL1, HFR1, and PIFs constitute a subset of antagonistic basic helix-loop-helix factors acting downstream of phyB and COP1 to regulate photomorphogenic development.