bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feasibility study of a randomised controlled trial to investigate the effectiveness of using a humanoid robot to improve the social skills of children with autism spectrum disorder (Kaspar RCT): a study protocol
Authors: Mengoni Silvana E , Irvine Karen , Thakur Deepshikha , Barton Garry , Dautenhahn Kerstin , Guldberg Karen , Robins Ben , Wellsted David , Sharma Shivani 
Published: June 2017

IntroductionInterventions using robot-assisted therapy may be beneficial for the social skills development of children with autism spectrum disorder (ASD); however, randomised controlled trials (RCTs) are lacking. The present research aims to assess the feasibility of conducting an RCT evaluating the effectiveness of a social skills intervention using Kinesics and Synchronisation in Personal Assistant Robotics (Kaspar) with children with ASD.Methods and analysisForty children will be recruited. Inclusion criteria are the following: aged 5–10 years, confirmed ASD diagnosis, IQ over 70, English-language comprehension, a carer who can complete questionnaires in English and no current participation in a private social communication intervention. Children will be randomised to receive an intervention with a therapist and Kaspar, or with the therapist only. They will receive two familiarisation sessions and six treatment sessions for 8 weeks. They will be assessed at baseline, and at 10 and 22 weeks after baseline. The primary outcome of this study is to evaluate whether the predetermined feasibility criteria for a full-scale trial are met. The potential primary outcome measures for a full-scale trial are the Social Communication Questionnaire and the Social Skills Improvement System. We will conduct a preliminary economic analysis. After the study has ended, a sample of 20 participants and their families will be invited to participate in semistructured interviews to explore the feasibility and acceptability of the study’s methods and intervention.Ethics and disseminationParents/carers will provide informed consent, and children will give assent, where appropriate. Care will be taken to avoid pressure or coercion to participate. Aftercare is available from the recruiting NHS Trust, and a phased withdrawal protocol will be followed if children become excessively attached to the robot. The results of the study will be disseminated to academic audiences and non-academic stakeholders, for example, families of children with ASD, support groups, clinicians and charities.Trial registration numberISRCTN registry (ISRCTN14156001); Pre-results.
Immune-mediated effects targeting hepatitis C virus in a syngeneic replicon cell transplantation mouse model
Authors: Levander Sepideh , Holmström Fredrik , Frelin Lars , Ahlén Gustaf , Rupp Daniel , Long Gang , Bartenschlager Ralf , Sällberg Matti 
Published: June 2017

ObjectiveHCV is characterised by its ability to establish chronic infection in hepatocytes and to replicate in the presence of an inflammation. We mimicked this situation in vivo in immune-competent mice by syngeneic transplantation of HCV replicon-containing mouse hepatoma cells.DesignA total of 5 million H-2b positive Hep56.1D cells, carrying a subgenomic genotype (gt) 2a replicon (HCV replicon cells) or stably expressing comparable levels of the HCV NS3/4A protease/helicase complex (NS3/4A hepatoma cells), were injected subcutaneously into syngeneic H-2b-restricted mice. Kinetics of tumour growth, HCV RNA replication levels and HCV-specific immune responses were monitored. For immune monitoring, new H-2b-restricted cytotoxic T cell epitopes within the gt2a NS3/4A region were mapped. Immune mice were generated by DNA-based vaccination.ResultsHCV replicon and NS3/4A hepatoma cells generated solid tumours in vivo. Similar to what is seen in human HCV infection did HCV RNA replicate in the presence of inflammation. NS3/4A-specific CD8+ T cells seemed to transiently reduce HCV RNA levels. Both CD4+ and CD8+ T cells were required for protection against tumour growth. Vaccine-induced NS3/4A(gt2a)-specific T cells protected against HCV replicon tumours in wild-type, but not in HCV NS3/4A(gt1a)-transgenic mice with dysfunctional HCV-specific T cells. Importantly, as in human HCV infection, HCV replicon cells neither primed nor boosted a strong NS3/4A-specific T cell response.ConclusionSyngeneic transplantation of mouse HCV replicon cells into immune-competent animals mirrors many in vivo events in humans. This system is versatile and can be applied to any genetically modified H-2b-restricted mouse strain.
MCAM Mediates Chemoresistance in Small-Cell Lung Cancer via the PI3K/AKT/SOX2 Signaling Pathway
Authors: Tripathi Satyendra C. , Fahrmann Johannes F. , Celiktas Muge , Aguilar Mitzi , Marini Kieren D. , Jolly Mohit K. , Katayama Hiroyuki , Wang Hong , Murage Eunice N. , Dennison Jennifer B. , Watkins D. Neil , Levine Herbert , Ostrin Edwin J. , Taguchi Ayumu , Hanash Samir M. 
Published: June 2017

Abstract
Despite favorable responses to initial therapy, small-cell lung cancer (SCLC) relapse occurs within a year and exhibits resistance to multiple drugs. Because of limited accessibility of patient tissues for research purposes, SCLC patient-derived xenografts (PDX) have provided the best opportunity to address this limitation. Here, we sought to identify novel mechanisms involved in SCLC chemoresistance. Through in-depth proteomic profiling, we identified MCAM as a markedly upregulated surface receptor in chemoresistant SCLC cell lines and in chemoresistant PDX compared with matched treatment-naïve tumors. MCAM depletion in chemoresistant cells reduced cell proliferation and reduced the IC50 inhibitory concentration of chemotherapeutic drugs in vitro. This MCAM-mediated sensitization to chemotherapy occurred via SOX2-dependent upregulation of mitochondrial 37S ribosomal protein 1/ATP-binding cassette subfamily C member 1 (MRP1/ABCC1) and the PI3/AKT pathway. Metabolomic profiling revealed that MCAM modulated lactate production in chemoresistant cells that exhibit a distinct metabolic phenotype characterized by low oxidative phosphorylation. Our results suggest that MCAM may serve as a novel therapeutic target to overcome chemoresistance in SCLC. Cancer Res; 77(16); 4414–25. ©2017 AACR.
Combined BTK and PI3Kδ Inhibition with Acalabrutinib and ACP-319 Improves Survival and Tumor Control in CLL Mouse Model
Authors: Niemann Carsten U. , Mora-Jensen Helena I. , Dadashian Eman L. , Krantz Fanny , Covey Todd , Chen Shih-Shih , Chiorazzi Nicholas , Izumi Raquel , Ulrich Roger , Lannutti Brian J. , Wiestner Adrian , Herman Sarah E.M. 
Published: June 2017

Abstract
Purpose: Targeting the B-cell receptor (BCR) pathway with inhibitors of Bruton tyrosine kinase (BTK) and PI3Kδ is highly effective for the treatment of chronic lymphocytic leukemia (CLL). However, deep remissions are uncommon, and drug resistance with single-agent therapy can occur. In vitro studies support the effectiveness of combing PI3Kδ and BTK inhibitors.
Experimental Design: As CLL proliferation and survival depends on the microenvironment, we used murine models to assess the efficacy of the BTK inhibitor acalabrutinib combined with the PI3Kδ inhibitor ACP-319 in vivo. We compared single-agent with combination therapy in TCL1-192 cell–injected mice, a model of aggressive CLL.
Results: We found significantly larger reductions in tumor burden in the peripheral blood and spleen of combination-treated mice. Although single-agent therapy improved survival compared with control mice by a few days, combination therapy extended survival by over 2 weeks compared with either single agent. The combination reduced tumor proliferation, NF-κB signaling, and expression of BCL-xL and MCL-1 more potently than single-agent therapy.
Conclusions: The combination of acalabrutinib and ACP-319 was superior to single-agent treatment in a murine CLL model, warranting further investigation of this combination in clinical studies. Clin Cancer Res; 23(19); 5814–23. ©2017 AACR.
T-cell Receptors for Clinical Therapy: In Vitro Assessment of Toxicity Risk
Authors: Kunert Andre , Obenaus Matthias , Lamers Cor H.J. , Blankenstein Thomas , Debets Reno 
Published: June 2017

Abstract
Adoptive therapy with T-cell receptor (TCR)–engineered T cells has shown promising results in the treatment of patients with tumors, and the number of TCRs amenable for clinical testing is expanding rapidly. Notably, adoptive therapy with T cells is challenged by treatment-related side effects, which calls for cautious selection of target antigens and TCRs that goes beyond their mere ability to induce high T-cell reactivity. Here, we propose a sequence of in vitro assays to improve selection of TCRs and exemplify risk assessments of on-target as well as off-target toxicities using TCRs directed against cancer germline antigens. The proposed panel of assays covers parameters considered key to safety, such as expression of target antigen in healthy tissues, determination of a TCR's recognition motif toward its cognate peptide, and a TCR's cross-reactivity toward noncognate peptides. Clin Cancer Res; 23(20); 6012–20. ©2017 AACR.
The Most Beautiful Body: The Physical Dimension in Martyrdom Narratives
Authors: Denaro Roberta 
Published: June 2017

Within the vast bibliography devoted to martyrdom in Islam the issue of the martyr’s corporeity has received comparatively little attention.
This article focuses on the exceptional features medieval texts ascribed to martyrs’ bodies, especially after their death on the battlefield. It examines a set of topoi through which Islamic religious literature differentiated these martyrs from other dead, using a sublimate and extraordinary corporeity as a sign of their spiritual excellence. Finally, the article takes into account some extreme developments of this attitude, well-represented in a ḥadīṯ (collected in Ibn al-Mubārak’s Kitāb al-ǧihād) stating that the martyr will be given a new, most beautiful, body immediately after death.
In the conclusion the article raises the question of the relevance of these themes to contemporary representations of martyrdom where images of martyrs’ bodies play a central role in the quest for legitimacy of religious, national or political communities.
Minimum 20 Year Follow-Up of Semi-Constrained Total Ankle Arthroplasty
Authors: Hartog Taylor Den , Carlson Samuel , Alvine Greg , Alvine Frank , Hartog Bryan Den , Callaghan John 
Published: June 2017

Category: Ankle Arthritis Introduction/Purpose: With the introduction of newer generations of total ankle arthroplasty (TAA) constructs, the incidence of TAA in the United States has been increasing. While TAA has emerged as an alternative to ankle arthrodesis for the management of end-stage ankle arthritis, long-term data evaluating clinical outcomes and the survivorship of ankle prostheses is lacking. The purpose of this study was to report the clinical outcomes and radiographic survivorship of a second-generation, semi-constrained titanium and cobalt-chromium total ankle prosthesis at minimum twenty-year follow-up in order to provide a benchmark comparison for future generations of TAA design. Methods: 132 total ankle replacements in 126 patients were performed by a single surgeon between July 1984 and October 1994. Follow-up evaluation consisted of determining revision status, completion of the validated ankle osteoarthritis scale, a short questionnaire, and a review of the available radiographs. All radiographs were evaluated for evidence of progressive radiolucent lines, osteolysis and component subsidence. Results: At minimum twenty-year follow-up, 37 patients were alive, 89 were deceased, and 5 were lost to follow-up. For living patients, average clinical follow up was 25.3 years. Average radiographic follow-up was 21.4 years. Over the minimum 20 year follow-up, 29 ankles were revised (23%). For living patients, 13 ankles were revised (35%). Conclusion: Twenty-three percent of all patients and 35% of living patients required a revision over the minimum 20 year follow up interval. 65% of living patients have retained their prosthesis and 75% of the entire cohort are still functioning with their original ankle replacement or died with the original ankle replacement in place. This study should provide a benchmark for newer designs when they obtain this length of follow-up.
12-HETrE inhibits platelet reactivity and thrombosis in part through the prostacyclin receptor
Authors: Tourdot Benjamin E. , Adili Reheman , Isingizwe Zitha R. , Ebrahem Meral , Freedman J. Cody , Holman Theodore R. , Holinstat Michael 
Published: June 2017

Key Points
The antiplatelet effects of 12-HETrE in humans and mice are partly dependent on IP in vitro. The antithrombotic effects of 12-HETrE are partially dependent on IP in vivo in mice.
Rethinking self-reported measure in subjective evaluation of assistive technology
Authors: Hossain Gahangir 
Published: June 2017

AbstractSelf-reporting is used as a subjective measure of usability study of technology solutions. In assistive technology research, more than often the ‘a coordinator’ directly assist the ‘subject’ in the scoring process. This makes the rating process slower and also introduces bias, such as, ‘Forer effect’ and/or ‘Hawthorne’ effect. To address these issues we propose to use technology mediated interaction between the ‘subject’ and ‘the coordinator’ in evaluating assistive technology solutions. The goal is to combine both the qualitative and quantitative scores to create a relatively unbiased rating system. Empirical studies were performed on two different datasets in order to illustrate the utility of the proposed approach. It was observed that, the proposed hybrid rating is relatively unbiased for usability study.
Anticancer activity of drug-loaded calcium phosphate nanocomposites against human osteosarcoma
Authors: Son Kyoung Dan , Kim Young-Jin 
Published: June 2017

Abstract

Background
Calcium phosphate (CaP) based nanoparticles are considered to be ideal drug carriers for delivery of anticancer drugs because of their excellent biocompatibility and pH responsiveness. However, CaP nanoparticles have the problems of limited drug load capacity, initial burst release, and short-term release. Thus, we prepared the CaP nanocomposites containing anticancer drug such as caffeic acid (CA-NP), chlorogenic acid (CG-NP), or cisplatin (CP-NP) in the presence of alginate as a polymer template to control the release rate of drugs.

Results
The drug-loaded CaP nanocomposites exhibited spherical shape with a size of under 100 nm and the size of nanocomposites was hardly affected by the addition of drug. UV-visible spectroscopic analysis confirmed the insertion of drug into the CaP nanocomposites. These nanocomposites showed an initial burst release of drug, followed by a prolonged release, in which the release profile of drugs was depended on the solution pH. In addition, the drug-loaded CaP nanocomposites revealed anticancer activity on human osteosarcoma in a manner dependent on concentration of drugs and time.

Conclusions
The drug-loaded CaP nanocomposites can contribute to the development of a new generation of controlled drug release carriers for chemotherapy of cancers.
In situ measurement of velocity-stress sensitivity using crosswell continuous active-source seismic monitoring
Authors: Marchesini Pierpaolo , Ajo-Franklin Jonathan B. , Daley Thomas M. 
Published: June 2017

The ability to characterize time-varying reservoir properties, such as the state of stress, has fundamental implications in subsurface engineering, relevant to geologic sequestration of [Formula: see text]. Stress variation, here in the form of changes in pore fluid pressure, is one factor known to affect seismic velocity. Induced variations in velocity have been used in seismic studies to determine and monitor changes in the stress state. Previous studies conducted to determine velocity-stress sensitivity at reservoir conditions rely primarily on laboratory measurements of core samples or theoretical relationships. We have developed a novel field-scale experiment designed to study the in situ relationship between pore-fluid pressure and seismic velocity using a crosswell continuous active-source seismic monitoring (CASSM) system. At the Cranfield, Mississippi, [Formula: see text] sequestration field site, we actively monitored seismic response for five days with a temporal resolution of 5 min; the target was a 26 m thick injection zone at approximately 3.2 km depth in a fluvial sandstone formation (lower Tuscaloosa Formation). The variation of pore fluid pressure was obtained during discrete events of fluid withdrawal from one of the two wells and monitored with downhole pressure sensors. The results indicate a correlation between decreasing CASSM time delay (i.e., velocity change for a raypath in the reservoir) and periods of reduced fluid pore pressure. The correlation is interpreted as the velocity-stress sensitivity measured in the reservoir. This observation is consistent with published laboratory studies documenting a velocity ([Formula: see text]) increase with an effective stress increase. A traveltime change ([Formula: see text]) of 0.036 ms is measured as the consequence of a change in pressure of approximately 2.55 MPa ([Formula: see text]). For [Formula: see text] total traveltime, the velocity-stress sensitivity is [Formula: see text]. The overall results suggest that CASSM measurements represent a valid technique for in situ determination of velocity-stress sensitivity in field-scale monitoring studies.
Enhancement of Hybrid SPEEK Based Polymer–Cyclodextrin-Silica Inorganic Membrane for Direct Methanol Fuel Cell Application
Authors: Kusworo Tutuk Djoko , Hakim Muhammad Fahmi , Hadiyanto H 
Published: June 2017

Direct methanol fuel cell (DMFC) is one of several types of fuel cells that use proton exchange membrane (PEM) as a liaison between the reaction at the cathode and anode. Polyether-ether ketone (PEEK) is one of the aromatic polymer that can be applied in DMFC because of its characteristics that are resistant to DMFC environment. The polymer is also quite easy in the sulfonation process using concentrated sulfuric acid. However the role of polyether-ether ketone as DMFC membrane material is still lack of advantage due to its low conductivity and therefore the modification is required to increase the value of proton conductivity of the membrane. The purpose of this experiment is to modify the membrane (sPEEK) with the addition of cyclodextrins-silica, additive variation charge of 2%, 6% and 10%, time and temperature were fixed at 4 hours and 65oC. The results showed the best results of membrane sPEEK was obtained at the addition of -cyclodextrin -silica 10% with the membrane characteristics of ion exchange capacity of 2.19 meq / g polymer, the degree of sulfonation of 81%, methanol permeability of 3.09 x 10-9 cm2 / s and water uptake membrane of 64%. Keywords: Direct Methanol Fuel Cell, Poly(ether ether ketone), cyclodextrin-silica, sulfonation, ionic conductivity.Article History: Received January 18th 2017; Received in revised form April 21st 2017; Accepted June 22nd 2017; Available onlineHow to Cite This Article: Kusworo, T.D., Hakim, M.F. and Hadiyanto, H. (2017) Enhancement of Hybrid SPEEK Based Polymer–Cyclodextrin-Silica Inorganic Membrane for Direct Methanol Fuel Cell Application. International Journal of Renewable Energy Development, 6(2), 165-170.https://doi.org/10.14710/ijred.6.2.165-170
The structure of the tetanus toxin reveals pH‐mediated domain dynamics
Authors: Masuyer Geoffrey , Conrad Julian , Stenmark Pål 
Published: June 2017

AbstractThe tetanus neurotoxin (TeNT) is a highly potent toxin produced by Clostridium tetani that inhibits neurotransmission of inhibitory interneurons, causing spastic paralysis in the tetanus disease. TeNT differs from the other clostridial neurotoxins by its unique ability to target the central nervous system by retrograde axonal transport. The crystal structure of the tetanus toxin reveals a “closed” domain arrangement stabilised by two disulphide bridges, and the molecular details of the toxin's interaction with its polysaccharide receptor. An integrative analysis combining X‐ray crystallography, solution scattering and single particle electron cryo‐microscopy reveals pH‐mediated domain rearrangements that may give TeNT the ability to adapt to the multiple environments encountered during intoxication, and facilitate binding to distinct receptors.
An Efficient FLP-Based Toolkit for Spatiotemporal Control of Gene Expression in Caenorhabditis elegans
Authors: Muñoz-Jiménez Celia , Ayuso Cristina , Dobrzynska Agnieszka , Torres-Mendéz Antonio , Ruiz Patricia de la Cruz , Askjaer Peter 
Published: June 2017

Abstract
Site-specific recombinases are potent tools to regulate gene expression. In particular, the Cre (cyclization recombination) and FLP (flipase) enzymes are widely used to either activate or inactivate genes in a precise spatiotemporal manner. Both recombinases work efficiently in the popular model organism Caenorhabditis elegans, but their use in this nematode is still only sporadic. To increase the utility of the FLP system in C. elegans, we have generated a series of single-copy transgenic strains that stably express an optimized version of FLP in specific tissues or by heat induction. We show that recombination efficiencies reach 100% in several cell types, such as muscles, intestine, and serotonin-producing neurons. Moreover, we demonstrate that most promoters drive recombination exclusively in the expected tissues. As examples of the potentials of the FLP lines, we describe novel tools for induced cell ablation by expression of the PEEL-1 toxin and a versatile FLP-out cassette for generation of GFP-tagged conditional knockout alleles. Together with other recombinase-based reagents created by the C. elegans community, this toolkit increases the possibilities for detailed analyses of specific biological processes at developmental stages inside intact animals.
Organized environmental crimes: Trends, theory, impact and responses
Authors: Hübschle Annette , Faull Andrew 
Published: June 2017

Once considered peripheral and a green matter, wildlife crimes have moved up global security and policy agendas. The UN General Assembly, for example, adopted two resolutions to tackle wildlife crimes in 2015 and 2016. Meanwhile the South Africa and the Southern African Development (SADC) have declared wildlife trafficking a priority crime issue. Rhino poaching, in particular, has captured the attention of the public, international community and our national government. Less charismatic plant and wildlife species are also harvested and trafficked across the globe. The lesser-known pangolin is considered the most trafficked species while cycads constitute the most threatened plant species on the planet. The illegal or irregular extraction of natural resources, logging, mining, overfishing, trafficking of toxic, nuclear or electronic waste, and industrial dumping have all become areas of concern.