bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of Simparica Trio™, a novel chewable tablet containing sarolaner, moxidectin and pyrantel, against induced hookworm infections in dogs
Authors: Becskei Csilla , Thys Mirjan , Kryda Kristina , Meyer Leon , Martorell Susanna , Geurden Thomas , Dreesen Leentje , Fernandes Tiago , Mahabir Sean P. 
Published: March 2020

AbstractBackgroundAncylostomatids (‘hookworms’) are among the most important zoonotic nematode parasites infecting dogs worldwide.Ancylostoma caninumandUncinaria stenocephalaare two of the most common hookworm species that infect dogs. Both immature and adult stages of hookworms are voracious blood feeders and can cause death in young dogs before infection can be detected by routine fecal examination. Hence, treatment of both immature and adult stages of hookworms will decrease the risk of important clinical disease in the dog as well as the environmental contamination caused by egg-laying adults, which should reduce the risk of infection for both dogs and humans. The studies presented here were conducted to evaluate the efficacy of a novel, oral chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™), against induced larval (L4), immature adult (L5) and adultA. caninum, and adultU. stenocephalainfections in dogs.MethodsEight negative-controlled, masked, randomized laboratory studies were conducted. Two separate studies were conducted against each of the target parasites and stages. Sixteen or 18 purpose bred dogs, 8 or 9 in each of the two treatment groups, were included in each study. Dogs experimentally infected with the target parasite were dosed once on Day 0 with either placebo tablets or Simparica Trio™ tablets to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5.0 mg/kg pyrantel (as pamoate salt). Timing of dosing relative to parasite inoculation allowed for efficacy to be evaluated primarily against the target parasite stage. Worm counts were conducted 7 or 8 days after treatments during necropsy. Efficacy was based on the number of worms recovered at necropsy compared to placebo control.ResultsBased on geometric mean worm counts, efficacy of Simparica Trio™ was ≥ 98.4% against L4larval stage ofA. caninum, ≥ 99.8% against immature adult (L5)A. caninum, and 100% against adultA. caninumand adultU. stenocephala.ConclusionsThese studies confirm the efficacy of a single oral dose of a novel, chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against L4larval and immature adult (L5)A. caninum, and adultA. caninumandU. stenocephalainfections in dogs.
Evaluation of the speed of kill of a novel orally administered combination product containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against induced infestations of Ixodes scapularis on dogs
Authors: Holzmer Susan , Kryda Kristina , Mahabir Sean P. , Everett William 
Published: March 2020

Abstract
Background
The black-legged (or deer) tick, Ixodes scapularis, commonly infests dogs in the USA and is the vector of important zoonotic pathogens, including Borrelia burgdorferi, the causative agent of Lyme disease. Rapid onset of activity is important in reducing the feeding activity of ticks, thereby reducing the possibility of transmission of infections. The speed of kill of a novel oral combination product, Simparica Trio™ containing sarolaner, moxidectin and pyrantel was evaluated in a well-controlled laboratory study against an existing infestation and subsequent weekly induced infestations of I. scapularis ticks on dogs.

Methods
Dogs were allocated randomly based on host suitability tick counts to treatment with a single dose of either placebo or Simparica Trio™ at the minimum label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt). All dogs were infested with approximately 50 unfed adult I. scapularis ticks at a 1:1 sex ratio on Days −2, 7, 14, 21, 28 and 35. Tick counts were conducted at 8, 12 and 24 h after treatment on Day 0 and after each subsequent infestation.

Results
No treatment-related adverse events occurred during the study. Dogs in the placebo-treated group maintained adequate tick infestations for the duration of the study. Day 0 tick counts at 8 h after treatment with Simparica Trio™ were reduced relative to placebo against an existing infestation with efficacy of 67.5%, demonstrating that Simparica Trio™ started killing ticks soon after treatment. Efficacy was 98.4 % at 12 h and 99.4% at 24 h. Rapid speed of kill was maintained throughout the month, with efficacy of ≥ 94.2% at 24 h after re-infestation through Day 28.

Conclusions
A single dose of Simparica Trio™ administered orally to dogs at the minimum label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt) was safe and began to kill existing I. scapularis ticks within 8 h after treatment and resulted in ≥ 94.2% efficacy within 24 h against re-infestations for a month.
Simultaneous 166Ho/99mTc dual-isotope SPECT with Monte Carlo-based downscatter correction for automatic liver dosimetry in radioembolization
Authors: van Rooij R. , Braat A. J. A. T. , de Jong H. W. A. M. , Lam M. G. E. H. 
Published: March 2020

Abstract
Background
Intrahepatic dosimetry is paramount to optimize radioembolization treatment accuracy using radioactive holmium-166 microspheres (166Ho). This requires a practical protocol that combines quantitative imaging of microsphere distribution with automated and robust delineation of the volumes of interest. To this end, we propose a dual isotope single photon emission computed tomography (SPECT) protocol based on 166Ho therapeutic microspheres and technetium-99 m (99mTc) stannous phytate, which accumulates in healthy liver tissue. This protocol may allow accurate and automatic estimation of tumor-absorbed dose and healthy liver-absorbed dose. The current study focuses on a Monte Carlo-based reconstruction framework that inherently corrects for scatter crosstalk between the 166Ho and 99mTc imaging. To demonstrate the feasibility of the method, it is evaluated with realistic phantom experiments and patient data.

Methods
The Utrecht Monte Carlo System (UMCS) was extended to include detailed modeling of crosstalk interactions between 99mTc and 166Ho. First, 99mTc images were reconstructed including energy window-based corrections for 166Ho downscatter. Next, 99mTc downscatter in the 81-keV 166Ho window was Monte Carlo simulated to allow quantitative reconstruction of the 166Ho images. The accuracy of the 99mTc-downscatter modeling was evaluated by comparing measurements with simulations. In addition, the ratio between 99mTc and 166Ho yielding the best 166Ho dose estimates was established and the quantitative accuracy was reported.

Results
Given the same level of activity, 99mTc contributes twice as many counts to the 81-keV window than 166Ho, and four times as many counts to the 140-keV window, applying a 166Ho/99mTc ratio of 5:1 yielded a high accuracy in both 166Ho and 99mTc reconstruction. Phantom experiments revealed that the accuracy of quantitative 166Ho activity recovery was reduced by 10% due to the presence of 99mTc. Twenty iterations (8 subsets) of the SPECT/CT reconstructions were considered feasible for clinical practice. Applicability of the proposed protocol was shown in a proof-of-concept case.

Conclusion
A novel 166Ho/99mTc dual-isotope protocol for automatic dosimetry compensates accurately for downscatter and allows for the addition of 99mTc without compromising 166Ho SPECT image quality.
To translanguage or not to translanguage: Ideology, practice, and intersectional identities
Authors: Nagashima Yuzuko , Lawrence Luke 
Published: March 2020

Abstract
Translanguaging is an emerging research area within applied linguistics that blurs the lines between named languages used by bi- and multilingual language users and considers all languages to be part of the individual’s single semiotic repertoire. In parallel with this emergence, issues surrounding language teacher identities and emotion labor have also become prominent sites of research in applied linguistics. In this paper we adopt a unique two-stage qualitative research approach involving aspects of narrative knowledging and duoethnography in order to investigate the challenges and obstacles faced by teachers of English in implementing translanguaging practices in their personal and professional lives. By using intersectionality as an analytical tool, we found that the challenges to making use of translanguaging practices were intimately and intricately linked with personal identities and social context. The results suggest that decisions surrounding translanguaging practices can be seen as context-dependent, discursively produced constructions, rather than the cut and dried options that they have been presented as in previous literature.
Overstandin: Upscaling reading positions and rescaling texts/signs
Authors: Singh Jaspal Naveel 
Published: March 2020

AbstractOverstandin occurs when languagers upscale their reading positions to rescale the meanings of texts or signs according to their own intentions. While understanding is an important faculty for languagers and a central analytical category for applied linguistics research, it cannot fully grasp agency and creativity in complex languaging in postcolonial worlds. By focusing on processes of overstandin, this article shows how languagers assume an upscaled reading position from which they find opportunities to attack the form and function of a text/sign. Thereby they can destabilise the indexical equilibrium of a sign and show up the ambivalence of language. Understanding often erases this ambivalence. For this reason, the exposure of ambivalence through overstandin can be emancipative, especially in postcolonial thinking. I further argue that overstandin is emphasised in the dream-state – both conceptualised as a state of relative unconscious experiencing and a wish, desire, aspiration for an emancipated future. In the dream-state the signifier stands over the signified. Such processes of overstandin pose challenges to applied linguistics, which continues to rely on wake-state understanding as a central analytical category for its gaze and its methods and thereby reproduces hegemonic knowledge-power structures that have been put in place during Enlightenment, colonialism and current global modernities. This article suggests that an account of processes of overstandin as an agentive meaning-making of the epistemic hinterlands of the postcolonial, could rehabilitate ambivalence as an anthropological category for our discipline. My detour via dream-states is merely a rhetoric of the argument presented here and it should not be assumed that I suggest that applied linguists have to turn to mysticism or dream analysis in order to account for overstandin, scaling and indexical ambivalence. The oneiric rhetoric itself is an overstandin, which aims to challenge common-sense empiricism in our discipline.
Interactional regimes of sociolinguistic behaviour: An ethnographic exploration of the scales at play across the spaces of an asylum-seeking centre
Authors: Spotti Massimiliano 
Published: March 2020

AbstractDrawing on the notion of sociolinguistic scaling, the present contribution argues for an understanding of an asylum-seeking centre as a unit of inquiry in which sociolinguistic repertoires are played out during intercultural communicative encounters. The contribution shows how the centre’s spaces encapsulate time- and space-bound interactional regimes and language hierarchies. Taken as such, the different rooms that make up the centre, e. g. the office, the activity room and the corridor, all may seem neutral spaces where the daily lives of people unfold. However, each of these spaces invites, allows and dismisses various interactional sociolinguistic regimes that lead to micro-practices of inclusion and exclusion. The article concludes with a consideration on whether the homogeneous category ‘newly arrived migrant in need of civic integration’ authored by many governments across Europe, should not be re-evaluated, in light of the affordances of sociolinguistic scaling and digital literacy potentials that each of these newly arrived individuals have in stock in their repertoires.
The Economics of Enlightenment: Time Value of Knowledge and the Net Present Value (NPV) of Knowledge Machines, A Proposed Approach Adapted from Finance
Authors: Kashyap Ravi 
Published: March 2020

AbstractWe formulate one methodology to put a value or price on knowledge using well accepted techniques from finance. We provide justifications for these finance principles based on the limitations of the physical world we live in. We start with the intuition for our method to value knowledge and then formalize this idea with a series of axioms and models. To the best of our knowledge this is the first recorded attempt to put a numerical value on knowledge. The implications of this valuation exercise, which places a high premium on any piece of knowledge, are to ensure that participants in any knowledge system are better trained to notice the knowledge available from any source. Just because someone does not see a connection does not mean that there is no connection. We need to try harder and be more open to acknowledging the smallest piece of new knowledge that might have been brought to light by anyone from anywhere about anything.
Animal fat and glycerol bioconversion to polyhydroxyalkanoate by produced water bacteria
Authors: Sohail Rafeya , Jamil Nazia , Ali Iftikhar , Munir Sajida 
Published: March 2020

Abstract
Oil reservoirs contain large amounts of hydrocarbon rich produced water, trapped in underground channels. Focus of this study was isolation of PHA producers from produced water concomitant with optimization of production using animal fat and glycerol as carbon source. Bacterial strains were identified as Bacillus subtilis (PWA), Pseudomonas aeruginosa (PWC), Bacillus tequilensis (PWF), and Bacillus safensis (PWG) based on 16S rRNA gene sequencing. Similar amounts of PHA were obtained using animal fat and glycerol in comparison to glucose. After 24 h, high PHA production on glycerol and animal fat was shown by strain PWC (5.2 g/ L, 6.9 g/ L) and strain PWF (12.4 g/ L, 14.2 g/ L) among all test strains. FTIR analysis of PHA showed 3-hydroxybutyrate units. The capability to produce PHA in the strains was corroborated by PhaC synthase gene sequencing. Focus of future studies can be the use of lipids and glycerol on industrial scale.
A Framework for Designing Business-Acceleration Programs: A Case Study from Egypt
Authors: Ismail Ayman 
Published: March 2020

AbstractBusiness acceleration services are gaining popularity around the world. In this study, we put forward a framework and an iterative process for the design of acceleration programs. Based on literature from around the world and a case study of an acceleration program in Egypt, we develop a model that considers the process for designing, monitoring, and adjusting an acceleration program based on both internal and external considerations. In this study, we find that aspects such as the analysis of the external environment in the surrounding entrepreneurship ecosystem, and of the internal environment in the host institution’s capabilities, resources, and limitations, are important in guiding the design process. We also illustrate a comprehensive set of design parameters to be considered in the development of the acceleration program, including the program’s value proposition, sector focus, duration, service offering, resource intensity, partnerships, as well as the profile of the startups supported. In presenting this model, we aim to fill an important gap in research on how accelerators are designed and offer a framework substantiated by academic review that helps practitioners and policymakers avoid “copying and pasting” acceleration programs without careful attention to the local contexts and needs.
Investigation of the role of β-TrCP in growth hormone transduction defect (GHTD)
Authors: Kostopoulou Eirini , Rojas Gil Andrea Paola , Spiliotis Bessie E. 
Published: March 2020

Abstract

Background
Growth hormone(GH) and epidermal growth factor (EGF) stimulate cell growth and differentiation, and crosstalking between their signaling pathways is important for normal cellular development. Growth hormone transduction defect (GHTD) is characterized by excessive GH receptor (GHR) degradation, due to over-expression of the E3 ubiquitin ligase, cytokine inducible SH2-containing protein (CIS). GH induction of GHTD fibroblasts after silencing of messenger RNA (mRNA) CIS (siCIS) or with higher doses of GH restores normal GH signaling. β-Transducing-repeat-containing protein (β-TrCP), another E3 ubiquitin ligase, also plays a role in GHR endocytosis. We studied the role of β-TrCP in the regulation of the GH/GHR and EGF/EGF receptor (EGFR) pathways in normal and GHTD fibroblasts.

Materials and methods
Fibroblast cultures were developed from gingival biopsies of a GHTD (P) and a control child (C). Protein expression and cellular localization of β-TrCP were studied by Western immunoblotting and immunofluorescence, respectively, after: (1) GH 200 μg/L human GH (hGH) induction, either with or without silence CIS (siCIS), and (2) inductions with 200 μg/L GH or 1000 μg/L GH or 50 ng/mL EGF.

Results
After induction with: (1) GH200/siCIS, the protein expression and cytoplasmic-membrane localization of β-TrCP were increased in the patient, (2) GH200 in the control and GH1000 in the patient, the protein and cytoplasmic-membrane localization of β-TrCP were increased and (3) EGF, the protein expression and cytoplasmic-membrane localization of β-TrCP were increased in both the control and the patient.

Conclusions
(1) β-TrCP appears to be part of the negative regulatory mechanism of the GH/GHR and EGF/EGFR pathways. (2) There appears to be a negative correlation between β-TrCP and CIS. (3) In the control and GHTD patient, β-TrCP increases when CIS is suppressed, possibly as a compensatory inhibitor of the GH/GHR pathway.
3-Iodothyronamine and 3,5,3′-triiodo-L-thyronine reduce SIRT1 protein expression in the HepG2 cell line
Authors: Sacripanti Ginevra , Lorenzini Leonardo , Bandini Lavinia , Frascarelli Sabina , Zucchi Riccardo , Ghelardoni Sandra 
Published: March 2020

Abstract

Background
3-Iodothyronamine (T1AM) is an endogenous messenger chemically related to thyroid hormone. Recent results indicate significant transcriptional effects of chronic T1AM administration involving the protein family of sirtuins, which regulate important metabolic pathways and tumor progression. Therefore, the aim of this work was to compare the effect of exogenous T1AM and 3,5,3′-triiodo-L-thyronine (T3) chronic treatment on mammalian sirtuin expression in hepatocellular carcinoma cells (HepG2) and in primary rat hepatocytes at micromolar concentrations.

Materials and methods
Sirtuin (SIRT) activity and expression were determined using a colorimetric assay and Western blot analysis, respectively, in cells treated for 24 h with 1–20 μM T1AM or T3. In addition, cell viability was evaluated by the MTTtest upon 24 h of treatment with 0.1–20 μM T1AM or T3.

Results
In HepG2, T1AM significantly reduced SIRT 1 (20 μM) and SIRT4 (10–20 μM) protein expression, while T3 strongly decreased the expression of SIRT1 (20 μM) and SIRT2 (any tested concentration). In primary rat hepatocytes, T3 decreased SIRT2 expression and cellular nicotinamide adenine dinucleotide (NAD) concentration, while on sirtuin activity it showed opposite effects, depending on the evaluated cell fraction. The extent of MTT staining was moderately but significantly reduced by T1AM, particularly in HepG2 cells, whereas T3 reduced cell viability only in the tumor cell line.

Conclusions
T1AM and T3 downregulated the expression of sirtuins, mainly SIRT1, in hepatocytes, albeit in different ways. Differences in mechanisms are only observational, and further investigations are required to highlight the potential role of T1AM and T3 in modulating sirtuin expression and, therefore, in regulating cell cycle or tumorigenesis.
The effects of follicle-stimulating hormone receptor (FSHR) -29 and Ser680Asn polymorphisms in IVF/ICSI
Authors: Paschalidou Chrysa , Anagnostou Elli , Mavrogianni Despoina , Raouasnte Rami , Klimis Nikiforos , Drakakis Peter , Loutradis Dimitrios 
Published: March 2020

Abstract

Background
The aim of this study was to analyze two different polymorphisms, Ser680Asn and -29 (G>A) promoter polymorphism, of the follicle-stimulating hormone receptor (FSHR) gene, individually but also in combination, in a sample of Greek women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI).

Materials and methods
One hundred and forty-one women undergoing IVF or ICSI and 94 controls were genotyped by real-time polymerase chain reaction (RT-PCR) for the two FSHR polymorphisms. The association of the alleles with the clinical, biochemical and other parameters concerning the controlled ovarian stimulation (COS) protocol and outcome was investigated, as well as the pregnancy rate.

Results
The study of each polymorphism individually revealed a positive correlation of the SerSer genotype (Ser680Asn polymorphism) with higher luteinizing hormone (LH) levels on the third day of the menstrual cycle. On the other hand, the A allele for the -29 (G>A) promoter polymorphism correlated with the increased number and quality of cumulus-oocyte complexes (COCs). No differences were detected when the different genotypes of the two polymorphisms were combined – the population study was grouped according to the number of polymorphic alleles they carried (0–4 alleles). Women who presented all polymorphic alleles, AsnAsn/AA, exhibited the lowest LH levels (2.62 ± 0.68 mIU/L), but were rarely detected (n = 2, 1.4% of the studied population).

Conclusions
The data from this study reflect that the investigation of the combination of polymorphisms, such as FSHR -29 and Ser680Asn, could offer a valuable tool in order to evaluate and anticipate the outcome of the ovulation induction protocols, especially in the group of patients with failed attempts.