bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population Pharmacokinetic Study and Individual Dose Adjustments of High‐Dose Methotrexate in Chinese Pediatric Patients With Acute Lymphoblastic Leukemia or Osteosarcoma
Authors: Hui Ka Ho , Chu Ho Man , Fong Pui Shan , Cheng Wai Tsoi Frankie , Lam Tai Ning 
Published: December 2018

AbstractHigh‐dose methotrexate (>0.5 g/m2) is among the first‐line chemotherapeutic agents used in treating acute lymphoblastic leukemia (ALL) and osteosarcoma in children. Despite rapid hydration, leucovorin rescue, and routine therapeutic drug monitoring, severe toxicity is not uncommon. This study aimed at developing population pharmacokinetic (popPK) models of high‐dose methotrexate for ALL and osteosarcoma and demonstrating the possibility and convenience of popPK model–based individual dose optimization using R and shiny, which is more accessible, efficient, and clinician‐friendly than NONMEM. The final data set consists of 36 ALL (354 observations) and 16 osteosarcoma (585 observations) patients. Covariate model building and parameter estimations were done using NONMEM and Perl‐speaks‐NONMEM. Diagnostic Plots and bootstrapping validated the models’ performance and stability. The dose optimizer developed based on the validated models can obtain identical individual parameter estimates as NONMEM. Compared to calling a NONMEM execution and reading its output, estimating individual parameters within R reduces the execution time from 8.7‐12.8 seconds to 0.4‐1.0 second. For each subject, the dose optimizer can recommend (1) an individualized optimal dose and (2) an individualized range of doses. For osteosarcoma, recommended optimal doses by the optimizer resemble the final doses at which the subjects were eventually stabilized. The dose optimizers developed demonstrated the potential to inform dose adjustments using a model‐based, convenient, and efficient tool for high‐dose methotrexate. Although the dose optimizer is not meant to replace clinical judgment, it provides the clinician with the individual pharmacokinetics perspective by recommending the (range of) optimal dose.
Caudal musculature in ground sharks, Carcharhiniformes, with remarks on their phylogenetic interrelationships
Authors: de Oliveira Lucas Romero , de Carvalho Marcelo Rodrigues , Soares Mateus Costa 
Published: December 2018

AbstractRelationships among families of the shark order Carcharhiniformes are still being debated, for example, in relation to the inclusion of hammerhead sharks (Sphyrnidae) and the tiger shark (Galeocerdo cuvier) in the Carcharhinidae. Previous morphological studies have not analyzed the phylogenetic significance of axial caudal muscles among carcharhiniforms. The authors therefore describe here the axial muscles of the tail region (m. epaxialis,m. obliquussuperioris,m. obliquusinferioris,m. flexor caudalis) to better understand their anatomical patterns among carcharhiniform sharks. Our results indicate that the family Pentanchidae, recently separated from scyliorhinids (catsharks), present a similar pattern of caudal muscles to catsharks, indicating their close phylogenetic relationship. Triakids, hemigaleids, leptochariids,Galeocerdo cuvierandPrionace glaucahave a unique pattern in which the medial axial bundle is bulkier than all other caudal axial muscles. Sphyrnids share with carcharhinids a similar pattern of them. obliquussuperioris(approximately the same size as the dorsalm. epaxialis) and have fibers of them. flexor caudalisarranged in a V‐shape. This chevron‐shape is also present on them. flexor caudalisof hemigaleids and leptochariids. Also, sphyrnids and carcharhinids have more slender septa between muscle bundles (more notably in carcharhinids; the only exception isGaleocerdo cuvier, which has the same pattern as sphyrnids). Although being used here as an outgroup, Squaliformes is unique in lacking one of the epaxial bundles. The authors conclude that the caudal axial musculature has greater phylogenetic potential than previously understood.
Quantitative susceptibility mapping detects neovascularization of the epiphyseal cartilage after ischemic injury in a piglet model of legg‐calvé‐perthes disease
Authors: Johnson Casey P. , Wang Luning , Tóth Ferenc , Aruwajoye Olumide , Kirkham Brooke , Carlson Cathy S. , Kim Harry K.W. , Ellermann Jutta M. 
Published: December 2018

BackgroundLegg‐Calvé‐Perthes disease (LCPD) is a childhood hip disorder thought to be caused by disruption of blood supply to the developing femoral head. There is potential for imaging to help assess revascularization of the femoral head.PurposeTo investigate whether quantitative susceptibility mapping (QSM) can detect neovascularization in the epiphyseal cartilage following ischemic injury to the developing femoral head.Study TypeProspective.Animal ModelRight femoral head ischemia was surgically induced in 6‐week‐old male piglets. The animals were sacrificed 48 hours (n = 3) or 4 weeks (n = 7) following surgery, and the operated and contralateral control femoral heads were harvested for ex vivo MRI.Field Strength/SequencePreclinical 9.4T MRI to acquire susceptibility‐weighted 3D gradient echo (GRE) images with 0.1 mm isotropic spatial resolution.AssessmentThe 3D GRE images were used to manually segment the cartilage overlying the femoral head and were subsequently postprocessed using QSM. Vessel volume, cartilage volume, and vessel density were measured and compared between operated and control femoral heads at each timepoint. Maximum intensity projections of the QSM images were subjectively assessed to identity differences in cartilage canal appearance, location, and density.Statistical TestsPaired t‐tests with Bonferroni correction were used (P < 0.008 considered significant).ResultsIncreased vascularity of the epiphyseal cartilage following ischemic injury was clearly identified using QSM. No changes were detected 48 hours after surgery. Vessel volume, cartilage volume, and vessel density were all increased in the operated vs. control femoral heads 4 weeks after surgery (P = 0.001, 0.002, and 0.001, respectively). Qualitatively, the increase in vessel density at 4 weeks was due to the formation of new vessels that were organized in a brush‐like orientation in the epiphyseal cartilage, consistent with the histological appearance of neovascularization.Data ConclusionQSM can detect neovascularization in the epiphyseal cartilage following ischemic injury to the femoral head.Level of Evidence: 1Technical Efficacy: Stage 1J. Magn. Reson. Imaging 2019;50:106–113.
Role of Virtual Touch Tissue Imaging Quantification in the Assessment of Hepatic Sinusoidal Obstruction Syndrome in a Rat Model
Authors: Han Hao , Yang Jian , Li Xia , Zhuge Yu‐zheng , Zhu Cheng‐kai , Chen Jun , Fu Yao , Wu Min 
Published: December 2018

ObjectivesTo investigate the value of liver stiffness in rats with various degrees of hepatic sinusoidal obstruction syndrome (HSOS) induced by monocrotaline by comparing liver histopathologic findings.MethodsSeventy rats were randomly divided into a control group (n = 10), a low‐dose monocrotaline group (n = 30), and a high‐dose monocrotaline group (n = 30). After successful modeling, the liver shear wave velocity (SWV) by Virtual Touch tissue imaging quantification (Siemens Medical Solutions, Mountain View, CA) and the alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin levels of the groups were obtained on days 3 and 5, and the intergroup differences were compared. Liver histopathologic characteristics were analyzed to evaluate the degrees of HSOS, and the scores were recorded.ResultsOn days 3 and 5, the total bilirubin, AST, and ALT, levels and liver SWV in the low‐ and high‐dose groups were elevated; the portal vein velocity (PVV) of these groups was decreased compared with the control group; and the high‐dose rats showed higher serum AST and ALT levels than the low‐dose rats. The high‐dose rats had a lower PVV than the low‐dose rats at day 3. The liver SWV values had significant correlations with the histologic score and PVV. In a multivariate analysis, the liver SWV (β = 0.813; P < .001) was independently associated with the histopathologic score.ConclusionsLiver stiffness as measured by Virtual Touch tissue imaging quantification increases with the severity of HSOS and can be recommended as a marker for diagnosis and assessment of HSOS.
Impact of Varying Binary Solvent Gradients on the Solubility Parameters of Poly(3‐hexylthiophene)
Authors: Sharp Devin , Taylor Sarah , Andrews McKenna , Boucher David 
Published: December 2018

AbstractCurrent methods for estimating the solubility parameters (SPs) of a solute, particularly conjugated polymers and organic semiconductor moieties, suffer from theoretical and computational deficiencies that have led to many questions and investigations that seek improvement in solubility parameter theory. This investigation focuses on the variation of SPs of a protype conjugated polymer, poly(3‐hexylthiophene), using (1) different set of solvents and binary solvent mixtures having a broad range of chemical characteristics, and (2) multiple computational methodologies, for example, functional solubility parameter and Hansen solubility parameter approaches. The results reveal that the choice of solvents and the fitting methodology impact the empirical SPs when using the binary gradient method. The validity of the observed SPs and the relative contributions of the dispersion, polar, and hydrogen‐bonding interactions are further rationalized using linear solvation energy relationship modeling of the solubility data.
Which subsets of an infinite random graph look random?
Authors: Brian Will 
Published: December 2018

AbstractGiven a countable graph, we say a set A of its vertices is universal if it contains every countable graph as an induced subgraph, and A is weakly universal if it contains every finite graph as an induced subgraph. We show that, for almost every graph on , (1) every set of positive upper density is universal, and (2) every set with divergent reciprocal sums is weakly universal. We show that the second result is sharp (i.e., a random graph on will almost surely contain non‐universal sets with divergent reciprocal sums) and, more generally, that neither of these two results holds for a large class of partition regular families.
The Tarski irredundant basis theorem and the finite soluble groups
Authors: Lucchini Andrea , Moscatiello Mariapia 
Published: December 2018

AbstractDenote by and , respectively, the smallest and the largest cardinality of a minimal generating set of a finite group G. The Tarski irredundant basis theorem implies that for every k with there exist a minimal generating set , an index and in G such that is again a minimal generating set of G. In this case we say that is an immediate descendant of ω. There are several examples of minimal generating sets of cardinality smaller than which have no immediate descendant and so it appears an interesting problem to investigate under which conditions an immediate descendant exists. In this paper we discuss this problem in the case of finite soluble groups.
Modified single pedicle reverse adipofascial flap for fingertip reconstruction
Authors: Losco Luigi , Lo Torto Federico , Maruccia Michele , Di Taranto Giuseppe , Ribuffo Diego , Cigna Emanuele 
Published: December 2018

BackgroundHomodigital adipofascial flap is a well‐established method for treating a distal fingertip defect; nonetheless, its use has some limitations. Reconstruction of fingertip injuries, with radial or ulnar tissue loss, may lead to some difficulties in providing an adequate bone coverage. The standard bipedicled technique did not allow the flap to cover the bone exposure without excessive tension. In our series, the reverse adipofascial flap had a single pedicle. The modified technique, because of its improved degree of rotation, granted the flap to reach either radial or ulnar tissue losses.Patients and MethodsWe treated 15 fingertip amputations distal to the lunula (9 Allen's type II and 6 type III), the mean size of defects was 2.7 cm2 (range, 1.8–3.2 cm2), the mean age of patients was 44 years (range, 22–63 years). Quick Disabilities of the Arm, Shoulder, and Hand score and Visual Analogue Scale were evaluated along with a 2‐point discrimination test; the aesthetic satisfaction of the patients was estimated subjectively using a 5‐point Likert scale.ResultsMean flap size was 3.6 cm2 (range, 2.5–4.2 cm2), primary flap survival was observed in 14 out of 15 cases, partial flap necrosis was observed in 1 case, the nail grew in all fingers in about 6 months. Mean proximal and distal interphalangeal joint motion was 89° (range, 80°–100°) and 71° (range, 65°–80°), respectively. No complications were observed at the donor site. The median static 2‐point discrimination was 4.5 mm (range, 3–8 mm), the mean quick DASH score was 2.6 (range, 0–9.1). All patients returned to work within a mean of 4.4 weeks (range, 4–5 weeks). The follow‐up was 12 months.ConclusionsSingle pedicle reverse adipofascial flap is an effective technique. This modified procedure allows a wider degree of flap rotation; it represents the ultimate arrow in our bow to address some particular defect geometry.
Relative antigenicity of components in vascularized composite allotransplants: An experimental study of microRNAs expression in rat hind limb transplantation model
Authors: Oda Hiroki , Ikeguchi Ryosuke , Aoyama Tomoki , Ohta Souichi , Noguchi Takashi , Kaizawa Yukitoshi , Yurie Hirofumi , Takeuchi Hisataka , Mitsuzawa Sadaki , Yamamoto Koji , Matsuda Shuichi 
Published: December 2018

BackgroundSkin is considered to be the most antigenic component of all vascularized composite allotransplantation tissues. However, no studies have used methods other than histological assessment to analyze the relative antigenicity of various components. In this study, we analyzed gene expression to investigate the relative antigenicity of each component in the transplanted limb.MethodsSeven Brown Norway rats and 31 Lewis rats were assigned to two groups: an allograft group and a syngeneic (control) group. Brown Norway rats were used as the allogeneic donors, and Lewis rats were used as the syngeneic donors and recipients. About 13 recipients in the allograft group and 12 recipients in the control group were analyzed. Histological assessment was performed in 5 of the recipients in each group, and microRNA expression was analyzed in the remaining recipients, except for 1 recipient in the syngeneic group.ResultsIn the allograft group, the relative microRNA‐146a expression was significantly higher in skin (2.34 ± 0.44) than in muscle (1.25 ± 0.22; p = .034) and bone (1; p = .0081). In the allograft group, microRNA‐155 expression was significantly higher in skin (1.91 ± 0.18) than in bone (1; p = .010). Histological assessment showed that some skin tissue in the allograft group showed evidence of severe acute rejection.ConclusionsThe microRNA‐146a and microRNA‐155 seemed to reflect the relative antigenicity during acute rejection of transplanted limbs. Skin seemed to be more antigenic than muscle and bone in both the histological assessment and gene expression analysis.
Expanding the applications of the combined transverse upper gracilis and profunda artery perforator (TUGPAP) flap for extensive defects
Authors: Ciudad Pedro , Huang Tony Chieh‐Ting , Manrique Oscar J. , Agko Mouchammed , Sapountzis Stamatis , Nicoli Fabio , Diya Sabbagh M. , Pont Luis Parra , Moran Steven L. , Chen Hung‐Chi 
Published: December 2018

BackgroundThe medial thigh is a well‐hidden area. The two most common flaps from this area are the transverse upper gracilis (TUG) and profunda artery perforator (PAP) flaps. Herein, we explored the applications of combined TUGPAP flap to reconstruct large and complex defects in different regions.MethodsBetween November 2015 and May 2017, 28 patients who underwent reconstruction and extensive soft tissue coverage with the TUGPAP flap for the breasts, head and neck, and pelvi‐perineal regions were included. The defects size ranged from 22 to 29 × 6–8 cm. All flaps were based on the two pedicles: the medial circumflex femoral artery for TUG flap and the profunda artery perforator for PAP flap. They were each anastomosed to a set of recipient vessels. A “Y”‐shaped interposition vein graft (YVG) was used if only one recipient artery was available.ResultsThe harvested skin paddle had dimensions ranged from 20 to 30 × 6–9 cm and all flaps survived completely. Postoperative complications included one case each of donor and recipient site seroma, and one case of wound dehiscence. They were all successfully managed conservatively. During an average follow‐up period of 12.7 months, one patient reported permanent paresthesia in the donor site and another developed hypertrophic scar. All patients were able to resume daily activity without major concerns.ConclusionThe combined TUGPAP flap is a safe, effective, and a good alternative to the common workhorse flaps as it offers the potential for a large skin paddle and decent soft tissue volume with low donor site morbidity in a well‐concealed area.
On operator norm convergence in time‐dependent homogenisation problems
Authors: Waurick Marcus 
Published: December 2018

AbstractUsing the d‐dimensional wave equation as a prime example, we shall show that an elementary functional analytic theorem for compact operators leads to operator norm convergence of the solution operators of the homogenisation for the wave equation considered as operators in space‐time. The results imply convergence of the amplitude functions locally in L2 with respect to the temporal and globally in L2 with respect to the spatial variables.
Application of the Finite Cell Method to Tunnel Engineering Simulation
Authors: Bui Hoang‐Giang , Meschke Günther , Schillinger Dominik 
Published: December 2018

AbstractThe Finite Cell Method (FCM) is an embedded domain method, in which the simulation domain is divided into a physical domain and a fictitious domain. The adaptive quadrature scheme employs the quad‐tree (oct‐tree in 3D) data structure to generate the quadrature points up to the specified level around the material boundary. In this paper, the FCM is applied for machine driven tunnel advancement simulations [1]. The geometry of the excavation volume is embedded into a background mesh by employing the B‐Rep concept. The mesh for the soil volume is structured and is fixed during the tunnel advancement. The tunnel lining is embedded in the soil mesh as a surface mesh, which incorporates the shell element formulation. In terms of the material description, the soil is represented as a saturated two‐phase medium [2], which consists of the soil matrix and the pore water. The effective stress of the soil is governed by means of the elastoplastic Mohr‐Coulomb constitutive model. Selected numerical benchmarks are performed to demonstrate the performance of the proposed method.
On the Accuracy of the Element‐wise Jacobi Methods for PGEP
Authors: Matejaš Josip , Hari Vjeran 
Published: December 2018

AbstractWe analyze the relative accuracy of two new element‐wise Jacobi‐type methods for the positive definite generalized eigenvalue problem Ax = λBx, where A and B are symmetric matrices and B is positive definite. A detailed error analysis is used, and the appropriate numerical tests are performed. If A and B are well‐behaved positive definite matrices then the transformation parameters will have small relative errors and numerical tests indicate the high relative accuracy of the methods.
Residence time optimization of spin pack polymer distributors
Authors: Hohmann Raphael , Leithäuser Christian 
Published: December 2018

AbstractWe consider the optimal shape design of polymer distributors used for industrial fiber spinning. In this laminar flow problem the residence time, the volume‐averaged age distribution of the fluid particles, has to be controlled to avoid material degradation. The residence time is modelled by an advection‐diffusion‐reaction equation with the fluid velocity being the transport field. This approach is more suitable for PDE‐constrained shape optimization than the Lagrangian particle‐tracking approach, where the observable is a finite set of trajectories. In order to develop an efficient shape optimization algorithm we derive the shape gradient of a tracking‐type cost functional by introducing the adjoint state.
Fault tolerant funnel control
Authors: Berger Thomas 
Published: December 2018

AbstractA new approach to adaptive fault tolerant tracking control for uncertain linear systems is presented. Based on recent results in funnel control and the time‐varying Byrnes‐Isidori form, we introduce a low‐complexity model‐free controller which achieves prescribed performance of the tracking error for any given sufficiently smooth reference signal. Within the considered system class, we allow for more inputs than outputs as long as a certain redundancy of the actuators is satisfied. An important role in the controller design is played by the controller weight matrix, which is a rectangular input transformation chosen such that in the resulting system the zero dynamics, which are assumed to be uniformly exponentially stable, are independent of the new input.
Funnel control for overhead crane model
Authors: Berger Thomas , Lê Huy Hoàng , Reis Timo 
Published: December 2018

AbstractWe consider an overhead crane whose control variables are the length of the rope and force/velocity at the gantry. The output consists of the position of the load. The objective is to design a closed‐loop tracking controller which also takes into account the transient behavior. First we show that this system has no well‐defined relative degree, which unfortunately does not allow to apply established methods for adaptive control to achieve the objective. To circumvent this problem, we design a dynamic state feedback which results in a system with relative degree four. Thereafter, we apply a funnel controller to this feedback system. We show that our approach can be used to move loads from one to another given position in the situation where there are several obstacles which have to be circumnavigated.
Thermally assembled shrink fit with annular inclusion and FGM‐hub
Authors: Apatay Tunç , Arslan Eray , Mack Werner 
Published: December 2018

AbstractSubject of the investigation is an elastic shrink fit with annular inclusion and functionally graded hub in a state of generalized plane strain. By appropriate grading both a substantial weight reduction and an improved performance at rotation can be achieved. In this contribution, special attention is paid also to the thermal assembly. In particular, numerical results are given for a steel/aluminum FGM‐hub.
Multiple goal‐oriented error estimates applied to 3d non‐linear problems
Authors: Endtmayer Bernhard , Langer Ulrich , Wick Thomas 
Published: December 2018

AbstractIn this work, we provide goal oriented error estimates for multiple (possibly) non‐linear functionals for a nonlinear partial differential equation. We combine the functionals in a certain way, and apply the dual weighted residual method using a partition of unity for localization. Finally, we provide a numerical example.