bluuebunny/crossref_metadata_2025_split huggingface dataset:
Limb specific Acvr1‐knockout during embryogenesis in mice exhibits great toe malformation as seen in Fibrodysplasia Ossificans Progressiva (FOP)
Authors: Hildebrand Laura , Schmidt‐von Kegler Mareen , Walther Maria , Seemann Petra , Stange Katja 
Published: March 2019

AbstractPurposeThis study analyzes Prx1‐specific conditional knockout of Acvr1 aiming to elucidate the endogenous role of Acvr1 during limb formation in early embryonic development. ACVR1 can exhibit activating and inhibiting function in BMP signaling. ACVR1 gain‐of‐function mutations can cause the rare disease fibrodysplasia ossificans progressiva (FOP), where patients develop ectopic bone replacing soft tissue, tendons and ligaments.MethodsWhole‐mount in situ hybridization and skeletal preparations revealed that following limb‐specific conditional knockout of Acvr1, metacarpals and proximal phalanges were shortened and additional cartilage and bone elements were formed.ResultsThe analysis of a set of marker genes including ligands and receptors of BMP signaling as well as genes involved in patterning and tendon and cartilage formation, revealed temporal disturbances with distinct spatial patterns. The most striking result was that in the absence of Acvr1 in mesoderm precursor cells, first digits were drastically malformed.ConclusionIn FOP, malformation of big toes can serve as a first soft marker in diagnostics. The surprising similarities in phenotype between the described conditional knockout of Acvr1 and the FOP mouse model, indicates a natural inhibitory function of ACVR1. This represents a further step towards better understanding the role of Acvr1 and developing treatment options for FOP.
Transcranial direct current stimulation over the sensory‐motor regions inhibits gamma synchrony
Authors: Pellegrino Giovanni , Arcara Giorgio , Di Pino Giovanni , Turco Cristina , Maran Matteo , Weis Luca , Piccione Francesco , Siebner Hartwig Roman 
Published: March 2019

AbstractTranscranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique able to induce plasticity phenomena. Although tDCS application has been spreading over a variety of neuroscience domains, the mechanisms by which the stimulation acts are largely unknown. We investigated tDCS effects on cortical gamma synchrony, which is a crucial player in cortical function. We performed a randomized, sham‐controlled, double‐blind study on healthy subjects, combining tDCS and magnetoencephalography. By driving brain activity via 40 Hz auditory stimulation during magnetoencephalography, we experimentally tuned cortical gamma synchrony and measured it before and after bilateral tDCS of the primary sensory‐motor hand regions (anode left, cathode right). We demonstrated that the stimulation induces a remarkable decrease of gamma synchrony (13 out of 15 subjects), as measured by gamma phase at 40 Hz. tDCS has strong remote effects, as the cortical region mostly affected was located far away from the stimulation site and covered a large area of the right centro‐temporal cortex. No significant differences between stimulations were found for baseline gamma synchrony, as well as early transient auditory responses. This suggests a specific tDCS effect on externally driven gamma synchronization. This study sheds new light on the effect of tDCS on cortical function showing that the net effect of the stimulation on cortical gamma synchronization is an inhibition.
Testing the myth of fee‐for‐service and overprovision in health care
Authors: Di Guida Sibilla , Gyrd‐Hansen Dorte , Oxholm Anne Sophie 
Published: March 2019

AbstractPaying on the basis of fee‐for‐service (FFS) is often associated with a risk of overprovision. Policymakers are therefore increasingly looking to other payment schemes to ensure a more efficient delivery of health care. This study tests whether context plays a role for overprovision under FFS. Using a laboratory experiment involving medical students, we test the extent of overprovision under FFS when the subjects face different fee sizes, patient types, and market conditions. We observe that decreasing the fee size has an effect on overprovision under both market conditions. We also observe that patients who are harmed by excess treatment are at little risk of overprovision. Finally, when subjects face resource constraints but still have an incentive to overprovide high‐profit services, they hesitate to do so, implying that the presence of opportunity costs in terms of reduced benefits to other patients protects against overprovision. Thus, this study provides evidence that the risk of overprovision under FFS depends on fee sizes, patients' health profiles, and market conditions.
Weekly cisplatin chemotherapy dosing versus triweekly chemotherapy with concurrent radiation for head and neck squamous cell carcinoma
Authors: Morse Ryan T. , Ganju Rohit G. , TenNapel Mindi J. , Neupane Prakash , Kakarala Kiran , Shnayder Yelizaveta , Chen Allen M. , Lominska Christopher E. 
Published: March 2019

AbstractBackgroundTriweekly high‐dose cisplatin (100 mg/m2) with concurrent radiation therapy is the current standard of care in the definitive or appropriate postoperative setting in head and neck squamous cell carcinoma (HNSCC). We compared triweekly 100 mg/m2 with alternative weekly 40 mg/m2 and weekly <40 mg/m2 cisplatin regimens.MethodsFrom 2011 to 2016, 163 patients received concurrent cisplatin and intensity‐modulated radiotherapy for locally advanced HNSCC. Primary endpoints were overall survival (OS) and progression‐free survival.ResultsCisplatin weekly <40 mg/m2 showed inferior OS outcomes when compared to weekly 40 mg/m2 (P = 0.084) and triweekly 100 mg/m2 (P = 0.04) regimens.ConclusionOur study displayed inferior outcomes with weekly cisplatin doses under 40 mg/m2, suggesting the inferiority of low‐dose weekly chemotherapy and the need for ongoing randomized trials to further explore 40 vs 100 mg/m2 chemotherapy regimens.
Gas phase selective hydrogenation of phenylacetylene to styrene over Au/Al2O3
Authors: Wang Xiaodong , Keane Mark A 
Published: March 2019

AbstractBACKGROUNDTrace quantities of phenylacetylene can poison styrene polymerisation catalysts. The phenylacetylene content must be less than 10 ppm and selective hydrogenation (to styrene) is viewed as a viable process solution. High styrene selectivities have been achieved in batch liquid phase operations while a switch from conventional batch liquid to continuous gas phase reaction presents process advantages in terms of higher throughput and enhanced productivity. We aim to provide the first direct comparison of Au/Al2O3 and Pd/Al2O3 in gas phase continuous catalytic hydrogenation of phenylacetylene.RESULTSTemperature programme reduction (TPR) generated metal particles at the nano‐scale (mean size = 3.0–4.3 nm), with evidence of electron donation from the aluminium oxide (Al2O3) carrier. Pd/Al2O3 exhibited a greater specific hydrogen (H2) uptake capacity than Au/Al2O3 under reaction conditions to deliver appreciably higher turnover frequencies (TOF) for reaction in excess H2. Stepwise hydrogenation predominated over Au/Al2O3 with 100% selectivity to styrene at 353 K where an increase in temperature favoured subsequent hydrogenation to ethylbenzene. Under the same conditions, Pd/Al2O3 was non‐selective, activating styrene to generate ethylbenzene with a greater contribution of direct phenylacetylene hydrogenation to ethylbenzene at higher temperature.CONCLUSIONKinetic analysis has revealed stepwise phenylacetylene hydrogenation in excess H2 over Au/Al2O3 with 100% selectivity to styrene. Stepwise hydrogenation also prevailed over Pd/Al2O3 at the lower temperature but surface activation of styrene coupled with enhanced H2 dissociation generated significant ethylbenzene. Decreasing inlet H2/phenylacetylene (to 1 mol/mol) over Pd/Al2O3 lowered rate where the activity/selectivity profile overlapped that exhibited by Au/Al2O3 in excess H2. © 2019 Society of Chemical Industry
Investigation of forward osmosis performance and anti‐fouling properties of the novel hydrophilic polymer brush‐grafted TFC‐type FO membranes
Authors: Wang Lin , Ma Fuqing , Jia Jizhen , Lei Xiaobin , Zhao Xinzhen , Liu Changkun 
Published: March 2019

AbstractBACKGROUNDThe concentration polarization and membrane fouling are two important factors, which can greatly reduce the forward osmosis (FO) performance and the service life of membranes. Optimizing the supporting layer structure and improving the hydrophilicity of the supporting layer are effective means to improve the FO performance and the anti‐fouling performance of thin‐film composite (TFC)‐type membranes.RESULTSA novel hydrophilic TFC‐type FO membrane with a macroporous polymer‐brush‐grafted polysulfone (PSf) supporting layer was fabricated. The prepared TFC‐type FO membrane (g‐FO‐3) showed remarkable FO and anti‐fouling performance. The water flux of g‐FO‐3 (43.0 L m−2 h−1) was nearly 2.6 times the conventional TFC‐type PSf‐based FO membrane (16.8 L m−2 h−1) and 1.8 times the TFC‐type FO membrane with macroporous PSf supporting layer but without polymer grafting (24 L m−2 h−1) in AL‐DS mode (the active layer facing the draw solution), with water as the feed solution and 2 mol L−1 sodium chloride as the draw solution. In addition, the low Js/Jw value of g‐FO‐3 indicated an excellent separation selectivity. Furthermore, the FO membrane kept a water flux recovery rate of 95% after the eight‐cycle fouling tests.CONCLUSIONThe hydrophilic polymer‐brush‐grafted PSf macroporous supporting layer of the FO membrane provides a convenient and efficient means to improve the FO and the anti‐fouling performance of the TFC‐type FO membranes. © 2019 Society of Chemical Industry
Long non‐coding RNA MIR22HG inhibits cell proliferation and migration in cholangiocarcinoma by negatively regulating the Wnt/β‐catenin signaling pathway
Authors: Hu Xiahong , Tan Zhaoxia , Yang Yijiang , Yang Pinghui 
Published: March 2019

AbstractBackgroundCholangiocarcinoma (CCA) is one of the most common primary biliary malignant tumors with a high mortality. MIR22HG has been reported to act as a tumor‐suppressor gene in several types of cancers. However, the role and molecular regulatory mechanism of MIR22HG in CCA still remains unclear. The present study aimed to investigate the role and underlying mechanism of MIR22HG in CCA.MethodsThe expression of MIR22HG was detected by RT‐qPCR assayin CCA tissues and cells. CCK‐8, colony formation and transwell assays were performed to study the biological function of MIR22HG in CCA. Western blot and immunofluorescence assays were performed to detect the expression ofWnt/β‐catenin signaling pathway markers. In vivo assays were conducted to explore the biological role of MIR22HG.ResultsWe first found that MIR22HG expression was significantly down‐regulated in CCA tissues and cell lines. Moreover, MIR22HG expression was related to TNM stage and bore prognostic significance in CCA patients. Function experiments demonstrated that overexpression of MIR22HG inhibited cell proliferation, migration and invasion in CCA, whereas knockdown of MIR22HG caused the opposite result. It was found that MIR22HG negatively regulated mRNA and the expression levels of proteins in the Wnt/β‐catenin signaling pathway (β‐catenin, cyclin D1 and c‐myc). The effect of MIR22HG overexpression on CCA progression could be partly rescued by activating the Wnt/β‐catenin signaling pathway. MIR22HG suppressed CCA tumorigenesis in vivo.ConclusionsIn summary, the results of the present study show that MIR22HG repressed cell proliferation, migration and invasion in CCA by negatively regulating the Wnt/β‐catenin signaling pathway. MIR22HG may be a novel target for diagnosis and therapy in CCA.
Altered cortical morphology of visual cortex in adults with monocular amblyopia
Authors: Lu Lu , Li Qian , Zhang Lianqing , Tang Shi , Yang Xubo , Liu Longqian , Sweeney John A. , Gong Qiyong , Huang Xiaoqi 
Published: March 2019

BackgroundThe neural mechanism of amblyopia and its impact on the adult brain remain unclear. This hinders effective treatment for adults with this disease.PurposeTo investigate neuroanatomical differences in cortical morphometry between amblyopic adults and healthy controls, and to explore the structural covariance of abnormal morphometric changes.Study TypeProspective.PopulationTwenty‐one amblyopic adults and 34 healthy controls.Field Strength/Sequence3T MRI, T1‐weighted, MPRAGE sequence.AssessmentAll participants completed ophthalmologic exams to confirm the diagnosis of amblyopia or its absence in the healthy controls, including tests of ocular motility and dilation, fundus exam, autorefraction and synoptophore tests. Cortical volume, thickness, and surface area measurements were obtained using FreeSurfer software.Statistical TestsStatistical differences of MRI measures between amblyopic adults and healthy controls were identified using a general linear model with intracranial volume and age as covariates. Monte Carlo simulations were used to correct for multiple comparisons. The structural covariance of abnormal morphometric changes and the relationship between morphometric abnormalities and visual acuity of the amblyopic eye were examined.ResultsCompared with healthy controls, amblyopic adults showed reduced cortical volume in left lateral occipital cortex, and decreased cortical thickness in bilateral inferior temporal gyrus and left precentral gyrus (P < 0.05; Monte Carlo corrected). Structural covariance between cortical volume of left lateral occipital cortex and cortical thickness of right inferior temporal gyrus in amblyopic adults was significantly less than in healthy controls (z = 1.73; P < 0.05).Data ConclusionOur study identified morphological abnormalities in occipital cortex and in temporal and frontal cortex which are projection fields of visual cortex important for processing of visual form and object location information, and disrupted structural covariance of visual cortex with other brain regions in amblyopic patients.Level of Evidence: 2Technical Efficacy: Stage 3J. Magn. Reson. Imaging 2019;50:1405–1412.
Standardization of volumetric modulated arc therapy‐based frameless stereotactic technique using a multidimensional ensemble‐aided knowledge‐based planning
Authors: Sarkar Biplab , Munshi Anusheel , Ganesh Tharmarnadar , Manikandan Arjunan , Anbazhagan Satheesh Kumar , Mohanti Bidhu Kalyan 
Published: March 2019

PurposeAim of this article is to describe a new knowledge‐based planning (KBP) methodology using volumetric modulated arc therapy (VMAT) for stereotactic radiosurgery (SRS) and radiotherapy (SRT) assisted by an ensemble mapping technique for use in a Monte Carlo planning system.MethodsLibraries of 121 stereotactic patients were assembled on the basis of eight different parameters (a) tumor laterality, (b) whether planning target volume (PTV) dose coverage challenged by the presence of the organ at risk (OAR), (c) prescription dose and number of fractions, (d) number of PTVs, (e) tumor volume, (f) shortest distance between OAR and PTV (edge to edge distance, or EED), (g) center to center distance between OARs and PTV (CCD), and (h) lateral dimension of external contour (brain). For new patients, the most appropriate library plan was selected on the basis of the above categorization. A KBP plan was created based on this selected library plan with all parameters unchanged keeping the isocenter at the center of PTV. Using the same beam configuration, another independent treatment plan (IP) was generated by an experienced dosimetrist for comparison. IP and KBP were compared for 76 new patients.ResultsOf 197 patients (121 library and 76 new), 103 (52.3%) were placed in the OAR‐challenged category and 94 were placed in the OAR unchallenged category. The ensemble mapping technique shows that, for an OAR‐challenged patient, picking up the library plan is appropriate. IP was marginally better than KBP in PTV coverage and dose conformity (PCI). Library plans, IP, and KBP offer a mean PCI of 0.77 ± 0.2, 0.79 ± 0.2, and 0.78 ± 0.4, mean PTV‐V99% of 97.3 ± 22.0%, 98.9 ± 14.1%, and 98.2 ± 13.2%, and mean MU of 2403.8 ± 2403.8, 2344.0 ± 2423.6, and 2473.6 ± 2296.8, respectively. Statistically significant differences were observed in the planning time between the IP and KBP plans for both OAR‐challenged (P < 0.001) and ‐unchallenged (P < 0.002) categories. Comparison of optimization and dose calculation time showed a much lower average planning time of 111.0 ± 84.1 min for KBP as against 248.2 ± 96.6 min for IP.ConclusionValidation results for KBP plans indicate the multidimensional ensemble mapping mechanism can accurately pick up the most appropriate library plan. KBP plans, although slightly inferior in their dosimetric quality, fulfill all the required clinical conditions and dose constraints. KBP plans save considerable planning time and are nearly independent of the skill and knowledge of the treatment planner. KBP works well with a Monte Carlo planning system like Monaco.
Construction of patient‐specific computational models for organ dose estimation in radiological imaging
Authors: Xie Tianwu , Akhavanallaf Azadeh , Zaidi Habib 
Published: March 2019

PurposeDiagnostic imaging procedures require optimization depending on the medical task at hand, the apparatus being used, and patient physical and anatomical characteristics. The assessment of the radiation dose and associated risks plays a key role in safety and quality management for radiation protection purposes. In this work, we aim at developing a methodology for personalized organ‐level dose assessment in x‐ray computed tomography (CT) imaging.MethodsRegional voxel models representing reference patient‐specific computational phantoms were generated through image segmentation of CT images for four patients. The best‐fitting anthropomorphic phantoms were selected from a previously developed comprehensive phantom library according to patient's anthropometric parameters, then registered to the anatomical masks (skeleton, lung, and body contour) of patients to produce a patient‐specific whole‐body phantom. Well‐established image registration metrics including Jaccard's coefficients for each organ, organ mass, body perimeter, organ‐surface distance, and effective diameter are compared between the reference patient model, registered model, and anchor phantoms. A previously validated Monte Carlo code is utilized to calculate the absorbed dose in target organs along with the effective dose delivered to patients. The calculated absorbed doses from the reference patient models are then compared with the produced personalized model, anchor phantom, and those reported by commercial dose monitoring systems.ResultsThe evaluated organ‐surface distance and body effective diameter metrics show a mean absolute difference between patient regional voxel models, serving as reference, and patient‐specific models around 4.4% and 4.5%, respectively. Organ‐level radiation doses of patient‐specific models are in good agreement with those of the corresponding patient regional voxel models with a mean absolute difference of 9.1%. The mean absolute difference of organ doses for the best‐fitting model extracted from the phantom library and Radimetrics™ commercial dose tracking software are 15.5% and 41.1%, respectively.ConclusionThe results suggest that the proposed methodology improves the accuracy of organ‐level dose estimation in CT, especially for extreme cases [high body mass index (BMI) and large skeleton]. Patient‐specific radiation dose calculation and risk assessment can be performed using the proposed methodology for both monitoring of cumulative radiation exposure of patients and epidemiological studies. Further validation using a larger database is warranted.
Solving partially observable agent‐intruder games with an application to border security problems
Authors: Laan Corine M. , Barros Ana Isabel , Boucherie Richard J. , Monsuur Herman , Timmer Judith 
Published: March 2019

AbstractIn this paper, we introduce partially observable agent‐intruder games (POAIGs). These games model dynamic search games on graphs between security forces (an agent) and an intruder given possible (border) entry points and high value assets that require protection. The agent faces situations with dynamically changing, partially observable information about the state of the intruder and vice versa. The agent may place sensors at selected locations, while the intruder may recruit partners to observe the agent's movement. We formulate the problem as a two‐person zero‐sum game, and develop efficient algorithms to compute each player's optimal strategy. The solution to the game will help the agent choose sensor locations and design patrol routes that can handle imperfect information. First, we prove the existence of ϵ‐optimal strategies for POAIGs with an infinite time horizon. Second, we introduce a Bayesian approximation algorithm to identify these ϵ‐optimal strategies using belief functions that incorporate the imperfect information that becomes available during the game. For the solutions of large POAIGs with a finite time horizon, we use a solution method common to extensive form games, namely, the sequence form representation. To illustrate the POAIGs, we present several examples and numerical results.
Forward‐in‐time goal‐oriented adaptivity
Authors: Muñoz‐Matute Judit , Pardo David , Calo Victor M. , Alberdi Elisabete 
Published: March 2019

SummaryIn goal‐oriented adaptive algorithms for partial differential equations, we adapt the finite element mesh to reduce the error of the solution in some quantity of interest. In time‐dependent problems, this adaptive algorithm involves solving a dual problem that runs backward in time. This process is, in general, computationally expensive in terms of memory storage. In this work, we define a pseudo‐dual problem that runs forward in time. We also describe a forward‐in‐time adaptive algorithm that works for some specific problems. Although it is not possible to define a general dual problem running forwards in time that provides information about future states, we provide numerical evidence via one‐dimensional problems in space to illustrate the efficiency of our algorithm as well as its limitations. Finally, we propose a hybrid algorithm that employs the classical backward‐in‐time dual problem once and then performs the adaptive process forwards in time.
Nanocomposites based on low density polyethylene filled with carbon nanotubes prepared by high energy ball milling and their potential antibacterial activity
Authors: Benigno Erika , Lorente Miguel A , Olmos Dania , González‐Gaitano Gustavo , González‐Benito Javier 
Published: March 2019

AbstractLow density polyethylene (LDPE) based nanocomposites containing multi‐walled carbon nanotubes (MWCNTs) were prepared by a two‐step process consisting of a pre‐mixture using high energy ball milling (HEBM) and subsequent hot pressing. The effects of ball milling and the presence of the MWCNTs on some physical properties of the materials and the antimicrobial efficiency against DH5α Escherichia coli were studied. Fourier transform infrared spectroscopy revealed that the polymer structure did not change in the final materials after the addition of MWCNTs and mixing. Differential scanning calorimetry showed small differences in the LDPE thermal behavior as a function of the type of material due to small changes in the polymer crystallization. This result was mainly ascribed to the milling process rather than to the incorporation of the MWCNTs. The presence of 1% by weight of the nanofiller increased the rigidity and hydrophobicity of the nanocomposites with respect to neat LDPE. This effect was explained by the preferential location of the MWCNTs in the surface of the material as the main factor decreasing the polar contribution to the surface free energy. A correlation between hydrophobicity, biofilm development and the shape and size of DH5α E. coli was observed, indicating that the presence of MWCNTs leads to a biocide effect by decreasing cell adhesion and changing its metabolism. © 2019 Society of Chemical Industry