bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics of Riluzole in Beagle Dogs
Authors: Perdigão Ana , Antunes Natalícia , Juni Lucas , de Freitas Noedi , Rojas-Moscoso Julio , Corrêa Sílvia , da Costa Ronaldo , Moreno Ronilson , Mendes Gustavo , De Nucci Gilberto 
Published: July 2018

Abstract
Background Riluzole is a benzothiazole anticonvulsant used in the treatment of patients with amyotrophic lateral sclerosis and it is being investigated for clinical use in patients with spinal cord injury. The present study evaluated the pharmacokinetics of riluzole in beagle dogs after oral dose administration.
Methods The oral doses (1.5, 5, 15 and 50 mg/kg) of riluzole were administered to beagle dogs and blood samples were collected from 0 h to 24 h post drug administration. Riluzole was quantified by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS).
Results The method was sensitive, precise, accurate and selective to riluzole quantification in plasma of beagle dogs. The pharmacokinetics following oral administration was linear from 1.5 to 15 mg/kg and the t1/2 was 2.16, 1.5, 1.8 and 3.0 h after oral administration of 1.5, 5.0, 15 and 50 mg/kg riluzole.
Conclusion The riluzole pharmacokinetics was linear up to 15 mg/kg and had a significantlyshorter t1/2 in beagle dogs than in humans.
Activation of the Intrinsic Pathway of Coagulation in Children with Meningococcal Septic Shock
Authors: Wuillemin Walter A , Fijnvandraat Karin , Derkx Bert H F , Peters Marjolein , Vreede Willem , ten Cate Hugo , Hack C Erik 
Published: July 2018

SummaryMeningococcal septic shock (MSS) is complicated by activation of coagulation, fibrinolytic, and complement systems. We studied the contact system of the intrinsic pathway of coagulation in thirteen children with MSS. Activation was assessed upon admittance to the intensive care unit and 48 h thereafter, based on the measurement of factor XII- (FXII), prekallikrein- and factor XI (FXI) antigen levels, as well as on the detection of FXIa-FXIa inhibitor, FXIIa-C1-inhibitor, and kallikrein-C1-inhibitor complexes, respectively. Levels of FXII, prekallikrein and FXI were reduced to about 50% in all patients on admission, and were significantly higher 48 h later. FXIIa-C1-inhibitor complexes were elevated in 7 patients, and kallikrein-C1-inhibitor complexes in 2 patients. FXIa-α1-antitrypsin complexes were elevated in all patients, FXIa-C1-inhibitor complexes in nine, and FXIa-anti-thrombin III complexes in one patient. We conclude that patients with MSS have activation of the contact system, which may contribute to activation of coagulation, and thus to morbidity and mortality.
Inactivation of Factor XIa in Vivo:
Studies in Chimpanzees and in Humans
Authors: Wuillemin Walter A , Hack C Erik , Bleeker Wim K , Biemond Bart J , Levi Marcel , Cate Hugo ten 
Published: July 2018

SummaryC1-inhibitor (C1Inh), antithrombin III (ATIII), α1-antitrypsin (a1AT), and α2-antiplasmin (a2AP) are known inhibitors of factor XIa (FXIa). However, their precise contribution to FXIa inactivation in vivo is not known. We investigated FXIa inactivation in chimpanzees and assessed the contribution of these inhibitors to FXIa inactivation in patients with presumed FXI activation.Chimpanzees were infused with FXIa and the various FXIa-FXIa inhibitor complexes formed were measured. Most of FXIa was complexed to C1Inh (68%), followed by a2AP (13%), a1AT (10%), and ATIII (9%). Analysis of the plasma elimination kinetics revealed a half-life time of clearance (t1/2) for the FXIa-FXIa inhibitor complexes of 95 to 104 min, except for FXIa-a1AT, which had a t1/2 of 349 min. Due to this long t1/2, FXIa-a1AT complexes were predicted to show the highest levels in plasma samples from patients with activation of FXI. This was indeed shown in patients with disseminated intravascular coagulation, recent myocardial infarction or unstable angina pectoris. We conclude from this study that in vivo C1Inh is the predominant inhibitor of FXIa, but that FXIa-a1 AT complexes due to their relatively long t1/2 may be the best parameter to assess FXI activation in clinical samples.
The Activity of Unfractionated Heparin and Low Molecular Weight Heparins in Rabbit Plasma – The Need for Using Absolute Anti-factor Xa and Antithrombin Activities
Authors: Peyrou V , Béguin S , Boneu B , Hemker H C 
Published: July 2018

SummaryRabbit being a common animal model to evaluate the antithrombotic effect of heparins, our purpose was to apply the heparin Standard Independent Unit (SIU) approach to rabbit plasma. To take into account the specificities of the enzymes we have measured the decay constants of factor Xa and of thrombin from autologous and heterologous origins, in presence and in absence of heparin. Different heparins or heparin fractions with a mean molecular weight from 1.7 to 10.5 kDa were used.We found that: a) the decay constants varied strongly between species and between enzymes; b) the decay constants of thrombin were always higher than those of factor Xa; c) the specific anti-factor Xa activity of heparins increased with the molecular weight and was 1.33 times higher when determined with bovine factor Xa than with rabbit factor Xa; d) the specific antithrombin activity of heparins also increased with the molecular weight but was similar when determined with rabbit and human thrombin; e) the specific anti-factor Xa activity was always lower than the specific antithrombin activity; f) the calibration of the heparins and heparin fractions against the 4th International Standard of Heparin expressed in International Units (IU) lead to a systematic overestimation of the anti-factor Xa activity and to an underestimation of the antithrombin activity.These observations indicate that it may be very important to use the SIU approach and to know the accurate activities to better understand the mechanism of the antithrombotic activity of heparins in experimental models.
Primary Allograft ACL Reconstruction in Skeletally Immature Patients—A Systematic Review of Surgical Techniques, Outcomes, and Complications
Authors: Shanmugaraj Ajaykumar , de SA Darren , Skelly Matthew M. , Duong Andrew , Simunovic Nicole , Musahl Volker , Peterson Devin C. , Ayeni Olufemi R. 
Published: July 2018

AbstractThe purpose of this systematic review is to ascertain the risk profile of allografts in primary anterior cruciate ligament reconstruction (ACLR) of skeletally immature patients. Three databases (PubMed, EMBASE, and MEDLINE) were searched for articles addressing primary ACLR in skeletally immature patients (i.e., open femoral and tibial physes). Inclusion criteria encompassed the use of allograft tissue with available postoperative outcomes data. The methodological index for non-randomized studies (MINORS) was used to assess all studies. Descriptive statistics such as means, 95% confidence intervals and standard deviations are presented where applicable. A total of 3,852 studies were screened, with 9 studies of a total of 406 skeletally immature patients (mean age 14.9 ± 1.2 years) satisfying inclusion criteria. The majority (98%) of included patients underwent complete transphyseal ACLR. Where specified, allograft options included Achilles tendon (AT) (66.5%), tibialis anterior tendon (7.6%), bone–patellar tendon (2.5%), and fascia lata (1.0%). The use of a bone block for the AT was reported in one patient (0.2%). Postoperatively, and where specified, patients achieved full range of motion (12.1%), had good Lysholm scores of 94 to 100 (8.1%), and a return to preinjury level athletic participation of 82.9% (8.4%). Complications (13.3%) included graft failures (7.9%), nonrevision reoperation (4.7%), and a combined leg length discrepancy and angular (valgus and extension) deformity (0.2%). There were no reported incidences of disease transmission. Although failure rates of primary allograft ACL reconstruction are acceptable compared with other studies of mainly autograft use in this young, high-risk population, there was a very low rate of clinically significant physeal damage. However, the relatively low quality of the included studies limits the ability to recommend routine use of allograft for ACLR in the skeletally immature patient. More robust studies with long-term follow-up data are necessary to better ascertain the influence of allograft choice on postoperative outcomes for these young patients. This is a Level IV study, systematic review of Levels III and IV studies.
Preoperative Opioid Use in Knee Surgery Patients
Authors: Meredith Sean J. , Nadarajah Vidushan , Jauregui Julio J. , Smuda Michael P. , Medina Shaun H. , Bennett Craig H. , Packer Jonathan D. , Henn R. Frank 
Published: July 2018

AbstractA cross-sectional analysis of data derived from patients undergoing knee surgery at a single institution was conducted. The objectives of the study were to determine the demographic, diagnostic, and psychologic factors associated with opioid use; and to determine the clinical correlates of opioid use. We hypothesized that preoperative opioid use would be associated with worse patient-reported outcome (PRO) measures. The sample consisted of 383 patients undergoing knee surgery. The patients were classified as either opioid or nonopioid users on the basis of medical record review. All participants completed a battery of clinical assessments, including the Patient-Reported Outcomes Measurement Information System computer adaptive testing in six domains: Physical Function, Pain Interference, Fatigue, Social Satisfaction, Anxiety, and Depression. Analyses were conducted to examine clinical variables as a function of opioid use. The results indicated that opioid use was associated with female gender, unemployment, smoking, higher American Society of Anesthesiologists scores, greater number of previous surgeries, depression or anxiety, and worse expectation of surgery (p < 0.05). Multivariable analysis found opioid use to be a significant independent predictor of multiple PRO measures in patients undergoing knee surgery. Potential explanations for these findings are presented, and clinical implications are discussed.
Heterogeneous Consumer Reactions to Health News
Authors: Browning Martin , Hansen Lars Gårn , Smed Sinne 
Published: July 2018

AbstractWe investigate heterogeneity in how consumers react to health‐related media information. Our specific focus is on news relating to fish and the consumption of different types of fish. We specify a dynamic empirical model that allows for pervasive heterogeneity in all basic parameters of consumer behavior, as well as in how consumers react to information. We estimate the model using a unique household panel tracking consumption, prices, news stories, and media habits over 24 quarters. We find that only 16% of consumers react to news that is specific to fatty fish. These consumers have a large reaction to such news, with a modest initial over‐reaction. Furthermore, these consumers are also more attentive to general media information about the healthiness of fish.
Recognition of CRISPR/Cas9 off-target sites through ensemble learning of uneven mismatch distributions
Authors: Peng Hui , Zheng Yi , Zhao Zhixun , Liu Tao , Li Jinyan 
Published: July 2018

Abstract

Motivation
CRISPR/Cas9 is driving a broad range of innovative applications from basic biology to biotechnology and medicine. One of its current issues is the effect of off-target editing that should be critically resolved and should be completely avoided in the ideal use of this system.

Results
We developed an ensemble learning method to detect the off-target sites of a single guide RNA (sgRNA) from its thousands of genome-wide candidates. Nucleotide mismatches between on-target and off-target sites have been studied recently. We confirm that there exists strong mismatch enrichment and preferences at the 5′-end close regions of the off-target sequences. Comparing with the on-target sites, sequences of no-editing sites can be also characterized by GC composition changes and position-specific mismatch binary features. Under this novel space of features, an ensemble strategy was applied to train a prediction model. The model achieved a mean score 0.99 of Aera Under Receiver Operating Characteristic curve and a mean score 0.45 of Aera Under Precision-Recall curve in cross-validations on big datasets, outperforming state-of-the-art methods in various test scenarios. Our predicted off-target sites also correspond very well to those detected by high-throughput sequencing techniques. Especially, two case studies for selecting sgRNAs to cure hearing loss and retinal degeneration partly prove the effectiveness of our method.

Availability and implementation
The python and matlab version of source codes for detecting off-target sites of a given sgRNA and the supplementary files are freely available on the web at https://github.com/penn-hui/OfftargetPredict.

Supplementary information
Supplementary data are available at Bioinformatics online.
fastp: an ultra-fast all-in-one FASTQ preprocessor
Authors: Chen Shifu , Zhou Yanqing , Chen Yaru , Gu Jia 
Published: July 2018

Abstract

Motivation
Quality control and preprocessing of FASTQ files are essential to providing clean data for downstream analysis. Traditionally, a different tool is used for each operation, such as quality control, adapter trimming and quality filtering. These tools are often insufficiently fast as most are developed using high-level programming languages (e.g. Python and Java) and provide limited multi-threading support. Reading and loading data multiple times also renders preprocessing slow and I/O inefficient.

Results
We developed fastp as an ultra-fast FASTQ preprocessor with useful quality control and data-filtering features. It can perform quality control, adapter trimming, quality filtering, per-read quality pruning and many other operations with a single scan of the FASTQ data. This tool is developed in C++ and has multi-threading support. Based on our evaluation, fastp is 2–5 times faster than other FASTQ preprocessing tools such as Trimmomatic or Cutadapt despite performing far more operations than similar tools.

Availability and implementation
The open-source code and corresponding instructions are available at https://github.com/OpenGene/fastp.
Discovering epistatic feature interactions from neural network models of regulatory DNA sequences
Authors: Greenside Peyton , Shimko Tyler , Fordyce Polly , Kundaje Anshul 
Published: July 2018

Abstract

Motivation
Transcription factors bind regulatory DNA sequences in a combinatorial manner to modulate gene expression. Deep neural networks (DNNs) can learn the cis-regulatory grammars encoded in regulatory DNA sequences associated with transcription factor binding and chromatin accessibility. Several feature attribution methods have been developed for estimating the predictive importance of individual features (nucleotides or motifs) in any input DNA sequence to its associated output prediction from a DNN model. However, these methods do not reveal higher-order feature interactions encoded by the models.

Results
We present a new method called Deep Feature Interaction Maps (DFIM) to efficiently estimate interactions between all pairs of features in any input DNA sequence. DFIM accurately identifies ground truth motif interactions embedded in simulated regulatory DNA sequences. DFIM identifies synergistic interactions between GATA1 and TAL1 motifs from in vivo TF binding models. DFIM reveals epistatic interactions involving nucleotides flanking the core motif of the Cbf1 TF in yeast from in vitro TF binding models. We also apply DFIM to regulatory sequence models of in vivo chromatin accessibility to reveal interactions between regulatory genetic variants and proximal motifs of target TFs as validated by TF binding quantitative trait loci. Our approach makes significant strides in improving the interpretability of deep learning models for genomics.

Availability and implementation
Code is available at: https://github.com/kundajelab/dfim.

Supplementary information
Supplementary data are available at Bioinformatics online.
Nontraditional Laboratory Animal Species (Cephalopods, Fish, Amphibians, Reptiles, and Birds)
Authors: O’Rourke Dorcas P , Baccanale Cecile L , Stoskopf Michael K 
Published: July 2018

AbstractAquatic vertebrates and cephalopods, amphibians, reptiles, and birds offer unique safety and occupational health challenges for laboratory animal personnel. This paper discusses environmental, handling, and zoonotic concerns associated with these species.
Three Infinities in Early Modern Philosophy
Authors: Schechtman Anat 
Published: July 2018

AbstractMany historical and philosophical studies treat infinity as an exclusively quantitative notion, whose proper domain of application is mathematics and physics. The main aim of this paper is to disentangle, by critically examining, three notions of infinity in the early modern period, and to argue that one—but only one—of them is quantitative. One of these non-quantitative notions concerns being or reality, while the other concerns a particular iterative property of an aggregate. These three notions will emerge through examination of three central figures in the period: Locke (for quantitative infinity), Descartes (ontic infinity), and Leibniz (iterative infinity).
High-throughput screening of biomolecules using cell-free gene expression systems
Authors: Contreras-Llano Luis E , Tan Cheemeng 
Published: July 2018

Abstract
The incorporation of cell-free transcription and translation systems into high-throughput screening applications enables the in situ and on-demand expression of peptides and proteins. Coupled with modern microfluidic technology, the cell-free methods allow the screening, directed evolution and selection of desired biomolecules in minimal volumes within a short timescale. Cell-free high-throughput screening applications are classified broadly into in vitro display and on-chip technologies. In this review, we outline the development of cell-free high-throughput screening methods. We further discuss operating principles and representative applications of each screening method. The cell-free high-throughput screening methods may be advanced by the future development of new cell-free systems, miniaturization approaches, and automation technologies.
In situ rumen degradation of kernels from short-season corn silage hybrids as affected by processing1,2
Authors: Miorin Renan L , Holtshausen Lucia , Baron Vern , Beauchemin Karen A 
Published: July 2018

Abstract
The objective of this in situ study was to evaluate the rumen degradability of kernels from short-season corn hybrids grown for silage in Western Canada (Lacombe, AB) and determine whether decreasing kernel particle size would enhance ruminal degradability in a similar manner for all hybrids. The study was a completely randomized design with 3 beef cows (replicates) and a 6 (hybrid) × 3 (particle size) factorial arrangement of treatments. Kernels were processed to generate three different particle sizes: large (2.3 mm), medium (1.4 mm), and small (0.7 mm). Processed samples were incubated in the rumen for 0, 3, 6, 12, 24, and 48 h using the in situ method and degradation kinetics of DM and starch were determined. Effective rumen degradability (ED) was estimated using a passage rate of 0.04 (ED4), 0.06 (ED6), and 0.08/h (ED8). Hybrids exhibited a range in whole plant DM content (23.7 to 25.0%), starch content (15.9 to 28.1% DM), kernel hardness (21.9 to 34.4 s/20 g) and density (3.57 to 4.18 g/mL), and prolamin content (8.24 to 11.34 g/100 g starch). Differences in digestion kinetics among hybrids were generally more pronounced for starch than DM. The hybrids differed in starch degradability (P &lt; 0.05), with earlier maturing hybrids having lower A fraction, lower kd, and lower ED, with hybrid effects on ED being accentuated with faster passage rate. Kernel DM content (r = −0.85, −0.87), hardness (r = −0.89, −0.86), and density (r = −0.84, −0.85) were negatively correlated with ED4 and ED8 of starch, respectively, due mainly to decreased kd of fraction B. Reducing the particle size of kernels increased ED of starch due to increased A fraction and kd of the B fraction. A tendency (P = 0.09) for hybrid × processing effects for ED6 and ED8 indicated that processing had greater effects on increasing ED of starch for earlier maturing hybrids. We conclude that short-season hybrids that mature early may have lower ED of DM and starch and would benefit from prolonged ensilage time. Kernel processing during silage making is recommended for short-season corn hybrids as a means of enhancing rumen availability of starch.
Feasibility of a Smartphone-based pilot intervention for Hispanic breast cancer survivors: a brief report
Authors: Buscemi Joanna , Buitrago Diana , Iacobelli Francisco , Penedo Frank , Maciel Crystal , Guitleman Judy , Balakrishnan Aparna , Corden Marya , Adler Rachel F , Bouchard Laura C , Perez-Tamayo Alejandra , Yanez Betina R 
Published: July 2018

Abstract
Hispanic breast cancer survivors (BCS) are at high risk for experiencing poor health-related quality of life (HRQoL) after completion of active breast cancer treatment. Therefore, there is a need to develop culturally tailored interventions for Hispanic BCS. To date, there have been limited interventions that have demonstrated that increasing cancer-related knowledge, self-efficacy in communication, and self-management skills can improve HRQoL among Hispanic BCS. These interventions have been delivered in person or by phone, which may be burdensome for Hispanic BCS. To facilitate intervention delivery, we developed My Guide, a Smartphone application aimed at improving HRQoL among Hispanic BCS. The purpose of the current study is to describe the feasibility results of a 4-week pilot trial testing My Guide among Hispanic BCS. Twenty-five women enrolled in the study (75% recruitment rate) and 22 women were retained (91.6% retention rate). Mean time spent using My Guide across the 4 weeks was 9.25 hr, and mean score on the satisfaction survey was 65.91 (range 42–70), in which higher scores reflect greater satisfaction. Participants’ scores on the Breast Cancer Knowledge Questionnaire significantly improved from study baseline (M = 9.50, SD = 2.92) to the postintervention assessment (M = 11.14, SD = 2.66), d = 0.59. Participants’ HRQoL scores improved over the course of 4 weeks, but these improvements were not statistically significant. Overall, My Guide was feasible and acceptable. Future studies will assess the preliminary efficacy of My Guide in improving HRQoL in a larger, randomized trial of Hispanic BCS.
Ilioinguinal Approach: Indication and Technique
Authors: Fensky Florian , Lehmann Wolfgang , Ruecker Andreas , Rueger Johannes M. 
Published: July 2018

Summary:
This video on the ilioinguinal approach presents its indications and techniques for the operative treatment of acetabular fractures. The principle of the ilioinguinal approach is to work through 3 different windows. The lateral window gives access to the pelvic bone from the sacroiliac joint to the lateral border of the iliopsoas muscle, the middle window accesses the medial border of the iliopsoas muscle to the femoral artery, and the medial window allows for control of the anterior pelvic ring medially from the femoral vein to the symphysis pubis. In this video, we demonstrate anatomical reconstruction of the acetabulum in a patient with an associated both-column fracture using the ilioinguinal approach. Indications are all acetabular fracture types, where in addition to anterior column fracture, a fractured posterior column is reducible through the middle window, that is, there is no involvement of the posterior column or wall that would necessitate a direct posterior approach. The ilioinguinal approach is a standard anatomical approach that gives an excellent visual and palpatory exposure of the anterior column up to the symphysis pubis and of the quadrilateral plate. Indications and techniques, how to develop this approach for the anatomical reduction and fixation of appropriate acetabular fractures, are demonstrated in this video.