bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mathematical, Mathematics Educational, and Educational Values in Mathematical Modeling Tasks
Authors: Dede Yüksel , Akçakın Veysel , Kaya Gürcan 
Published: June 2020

Purpose: The purpose of this study is to explore the mathematical values, mathematics educational values, and educational values involved in mathematical modeling tasks based on different mathematical modeling perspectives. Design/Approach/Methods: In this context, the present study is a qualitative research based on document analysis. The data were analyzed using semantic content analysis, and the selected modeling tasks based on different mathematical modeling perspectives were examined at the sentence level. Findings: Control, mystery, and openness mathematical values appeared in all mathematical modeling tasks, and rationalism and objectivism mathematical values appeared in realistic/applied and socio-critical modeling perspectives. Product, exploration, creating, relevance, pleasure, and application mathematics educational values also emerged in all modeling tasks. Educational values of social justice, equity, social welfare, humanity, and altruism were more important in the socio-critical modeling, while the value of individualism was more emphasized in the model-eliciting approach. Originality/Value: By determining mathematical, mathematics educational, and educational values involved in mathematical modeling tasks based on different mathematical modeling perspectives, an effective and more value-balanced mathematical modeling instruction can be provided.
Expedited Desensitization to Canakinumab
Authors: Sanan Neha , Schend Jason , Rowane Marija , Hostoffer Robert 
Published: June 2020

Introduction Interleukin-1 (IL-1) antagonists have been successful in the management of monogenic auto-inflammatory diseases, notably classic hereditary fever syndromes, such as Familial Mediterranean Fever (FMF). Anakinra (Kineret®), a human recombinant IL-1 receptor antagonist (IL-1Ra), has been clinically effective in the management of persistent auto-inflammation, such as FMF. Few studies report anaphylaxis in response to anakinra, which were resolved with an anakinra desensitization or the anti-IL-1β monoclonal antibody canakinumab (ILARIS®). We describe the first reported desensitization protocol to canakinumab. Case Report A 51-year-old man with a prior history of FMF presented with history of failed colchicine, nonsteroidal anti-inflammatory drug, and anakinra trials. Anakinra desensitization and canakinumab intradermal testing (IDT) resulted in anaphylactic and allergic symptoms, respectively. Expedited desensitization to canakinumab was successfully performed with 15-minute intervals between 13 doses of incremental increase to 150 mg. Discussion Biological agents are immune modulators that may evoke unanticipated hypersensitivity reactions, including anaphylaxis. These anaphylactic reactions to biologics have been infrequently reported, but the expanding market may increase the risk of IgE-mediated hypersensitivities and subsequent need for desensitization protocols. The current, expedited desensitization evaluated several published protocols involving anakinra desensitization to determine appropriate dosing for canakinumab. Conclusion We report the gastrointestinal intolerance and continued FMF flares on colchicine, followed by anaphylactic responses to anakinra and allergic reaction to IDT of canakinumab, in the present case of FMF. Our novel, expedited canakinumab desensitization protocol serves as an effective and alternative therapy in cases when other appropriate biologic agents are not tolerated.
Does Local Administration of Liposomal Bupivacaine Reduce Pain and Narcotic Consumption in Adult Spinal Deformity Surgery?
Authors: Chung Andrew S. , Crandall Dennis , Revella Jan , Adeniyi Biodun , Chang Yu Hui H. , Chang Michael S. 
Published: June 2020

Study Design: Retrospective cohort study. Objective: To determine if local administration of liposomal bupivacaine (LB) reduces postoperative pain scores and narcotic use in spinal deformity patients. Methods: Adult patients undergoing elective spinal fusion (7 or more levels) for scoliosis or kyphosis were selected for inclusion. Patients received either periincisional injections of combined liposomal and standard bupivacaine (n = 90, group L) or standard bupivacaine only (n = 69, group C). Perioperative pain scores (VAS [visual analogue scale]), opioid use, length of stay, functional outcome (ODI [Oswestry Disability Index]), and perioperative complications were recorded. No external funding was received for this study. Results: A total of 159 patients met inclusion criteria (mean age was 54.2 years of age). No significant baseline demographic differences were noted between the 2 groups. Group L experienced slight improvements in pain control on postoperative day (POD) 1 ( P = .02). No difference in pain scores were otherwise noted. Group L transitioned off of intravenous (IV) narcotics faster with 52.6% less IV use by POD3 ( P = .03). No differences in total narcotic consumption, perioperative complications, lengths of stay, and functional outcome scores were otherwise noted between the 2 cohorts. Conclusions: The use of LB in adult spinal deformity surgery does not appear to provide clinically important improvements in postoperative pain at the manufacturer’s recommended dosage. Furthermore, while patients receiving LB may transition more quickly off of IV narcotics, this does not appear to translate into an overall decrease in narcotic consumption, hasten return of bowel function, or decrease hospital lengths of stay. Future prospective randomized control trials are warranted. The use of varying dosages of LB may also help further clarify the true efficacy of LB in the setting of spinal deformity surgery.
Comparison of peripheral nerve block with local infiltration analgesia regarding walking ability after total knee replacement: A retrospective, propensity-score matched-pair cohort study
Authors: Fukuda Taeko , Imai Shinobu , Simoda Shunji , Nakdera Masaya , Horiguchi Hiromasa 
Published: June 2020

Purpose: It is unclear whether perioperative analgesic techniques affect the functional outcome of total knee replacement (TKR). We investigated the effects of peripheral nerve block (PNB) and local infiltration (LI) on walking ability after TKR. Methods: The medical records of 7143 patients who underwent TKR using general anesthesia with PNB or LI techniques were reviewed. Factors affecting independence and/or improvement of walking after surgery were investigated using multivariate regression analysis. To adjust for baseline differences and minimize selection bias for the chosen analgesic technique, patients were matched by propensity scores. Results: The multivariate regression analysis showed that PNB was associated with independence and/or improvement of walking. Of the 7143 patients, 2755 (39%) received PNB analgesia and 4388 (61%) LI analgesia. After the propensity score matching, the analgesic types were not associated with walking ability. Independence reflected by the total score of daily living activities was higher in the PNB group than in the LI group. The PNB group started rehabilitation later but performed rehabilitation for longer in the initial period than the LI group. Consumption levels of fentanyl, pentazocine, and antiemetics were lower in the PNB group than in the LI group. The PNB group had fewer hypertensive episodes during surgery than the LI group. There was no significant difference in total hospitalization costs between the two groups. Conclusions: No significant difference in postoperative walking ability was found between PNB and LI groups. However, PNB offered some advantages over LI. Future detailed investigations to improve TKR surgery are needed.
Acute Effects of Increased Joint Mobilization Treatment Duration on Ankle Function and Dynamic Postural Control in Female Athletes With Chronic Ankle Instability
Authors: Holland Christopher J. , Hughes Jonathan D. , De Ste Croix Mark B.A. 
Published: June 2020

Background: Chronic ankle instability (CAI) is linked to mechanical and functional insufficiencies. Joint mobilization is purported to be effective at treating these deficits. Purpose: To examine the effect of different treatment durations of a grade IV anterior-to-posterior ankle joint mobilization on weightbearing dorsiflexion range of motion (WB-DFROM), posterior talar glide (PG), and dynamic postural control in individuals with CAI. Study Design: Controlled laboratory study. Methods: A total of 48 female athletes (mean age, 22.8 ± 4.8 years) with unilateral CAI participated in this study. Participants were randomly assigned to 1 of 3 treatment conditions: 30 seconds, 60 seconds, and 120 seconds. Treatment was provided to the injured limb on 3 separate occasions 48 hours apart and consisted of a Maitland grade IV anterior-to-posterior talar joint mobilization based on the participant’s initial group assignment. WB-DFROM; PG; and the anterior (ANT), posteromedial (PM), and posterolateral (PL) reach directions of the Star Excursion Balance Test were measured bilaterally before and after each treatment. The uninjured limb acted as a control. Data were analyzed using 2-way mixed-model analyses of variance, and effect sizes were calculated through use of Hedges g. Results: Significant differences were detected after all treatment sessions for all outcome measures ( P ≤ .001) and between treatment groups after sessions 1, 2, and 3 for all outcome measures ( P ≤ .001). Effect sizes were very large or huge for all treatment groups for WB-DFROM, PG, and ANT reach direction. Substantial variation was found in effect sizes for PM and PL measures. Conclusion: Accessory mobilization is an effective treatment to induce acute changes in ankle motion and dynamic postural control in patients with CAI, with longer treatment durations conferring greater improvements. Clinical Relevance: This study adds clarity to the use of joint mobilization treatments and will add to the current clinical practice strategy for patients with CAI.
An Exploration of Knowledge and Attitudes of Medical Students and Rheumatologists to Placebo and Nocebo Effects: Threshold Concepts in Clinical Practice
Authors: Arnold Mark H , Finniss Damien , Luscombe Georgina M , Kerridge Ian 
Published: June 2020

Introduction: Understanding placebo and nocebo responses (context/meaning effects [CMEs]) is fundamental to physician agency. Specific instruction in CMEs is often lacking in medical education. Patient–practitioner interactions may challenge medical students’ understanding of biomedical causality and the nexus between this, practical ethics and professionalism across various conceptual and applied aspects of CMEs. This study compared the corpus of knowledge and phronesis related to CMEs between Australian graduate medical students and rheumatologists to gain a sophisticated understanding of this relationship to inform curriculum development. Method: In 2013 and 2014, the authors surveyed third-year medical students undertaking a graduate programme in an Australian medical school and Australian rheumatologists to ascertain their understanding of placebo and nocebo responses. The survey ascertained (1) the alignment of the respondents’ understanding of CMEs with accepted facts and concepts; (2) opinions on the ethical status of CMEs; and (3) responses to 2 scenarios designed to explore matters of biomedical causality, practical ethics and professionalism. Results: There were 88 completed surveys returned, 53 rheumatologists and 35 students. Similar proportions within each group identified CMEs, with most (n = 79/88 [89.8%]) correctly recognising a placebo (rheumatologists: 50 [94.3%], students: 29 [82.9%]) and approximately three-quarters (n = 65/88 [73.9%]) correctly recognising nocebo effects (rheumatologists: 39 [73.6%], students: 26 [74.3%]). Statistically significant differences between practitioners and students were observed in relation to the following: placebo responders and placebo responsiveness; placebos as a ‘diagnostic tool’; placebos usage in clinical practice and research, and nocebo effects. Conclusions: Physicians require an awareness of CMEs and the fact that they arise from and influence the effective agency of health care professionals. Curricular emphasis is needed to permit an honest assessment of the components that influence when, how and why patient outcomes arise, and how one’s agency might have neutral or negative effects but could be inclined towards positive and away from negative patient outcomes.
Development of Polymeric Micelles of Oleanolic Acid and Evaluation of Their Clinical Efficacy
Authors: An Joo Young , Yang Hee Seon , Park Na Rae , Koo Tae-sung , Shin Bungchul , Lee Eun Hee , Cho Sun Hang 
Published: June 2020

AbstractOleanolic acid has been used only as a subsidiary agent in cosmetic products. The aim of the study is to show the effect of oleanolic acid as an active ingredient for the alleviation of wrinkles in humans and to develop a polymeric micelle formulation that enables poorly soluble oleanolic acid to be used as a main ingredient in cosmetic products for reducing wrinkles. The solubility of oleanolic acid was evaluated in solubilizers, surfactants, and polymers. The particle sizes and shapes of polymeric micelles containing oleanolic acid were evaluated by electrophoretic light scattering spectrophotometer and scanning electron cryomicroscopy. Encapsulation efficiency and skin permeation were measured by HPLC. Stability of the polymeric micelles stored at 40 °C for 3 months was evaluated by visual observation, particle size measurement, and oleanolic acid content measurement. Polymeric micelles in final product ampoule form were applied around the eyes of 23 female subjects for 8 weeks. Five skin parameters were evaluated by optical profilometry every 4 weeks for 8 weeks. In addition, professionals made visual observations of the skin and a human skin irritation study was conducted. Polymeric micelles of oleanolic acid with a particle size of less than 100 nm were prepared using Capryol 90® and poloxamer. The skin permeation rate of the oleanolic acid in the polymeric micelles was higher than that in the other solutions made of oleanolic acid dispersed in 2 different surfactants. No significant changes in particle size, color, or oleanolic acid content were observed, and the polymeric micelles stored at 40 °C for 3 months did not undergo phase separation. After 8 weeks of application, skin irritation had not developed and all five parameters evaluated by optical profilometry as well as the visual evaluation scores were significantly improved. This study showed that the polymeric micelles of oleanolic acid prepared in this study were stable and effective at alleviating wrinkles in humans as the principal active ingredient. Based on these findings, it is expected that polymeric micelles of oleanolic acid can be widely used in cosmetic applications.
Effect of Root Colonization by Arbuscular Mycorrhizal Fungi on Growth, Productivity and Blast Resistance in Rice
Authors: Campo Sonia , Martín-Cardoso Héctor , Olivé Marta , Pla Eva , Catala-Forner Mar , Martínez-Eixarch Maite , San Segundo Blanca 
Published: June 2020

Abstract
Background
Arbuscular mycorrhizal (AM) fungi form symbiotic associations with roots in most land plants. AM symbiosis provides benefits to host plants by improving nutrition and fitness. AM symbiosis has also been associated with increased resistance to pathogen infection in several plant species. In rice, the effects of AM symbiosis is less studied, probably because rice is mostly cultivated in wetland areas, and plants in such ecosystems have traditionally been considered as non-mycorrhizal. In this study, we investigated the effect of AM inoculation on performance of elite rice cultivars (Oryza sativa, japonica subspecies) under greenhouse and field conditions, focusing on growth, resistance to the rice blast fungus Magnaporthe oryzae and productivity.

Results
The response to inoculation with either Funneliformis mosseae or Rhizophagus irregularis was evaluated in a panel of 12 rice cultivars. Root colonization was confirmed in all rice varieties. Under controlled greenhouse conditions, R. irregularis showed higher levels of root colonization than F. mosseae. Compared to non-inoculated plants, the AM-inoculated plants had higher Pi content in leaves. Varietal differences were observed in the growth response of rice cultivars to inoculation with an AM fungus, which were also dependent on the identity of the fungus. Thus, positive, negligible, and negative responses to AM inoculation were observed among rice varieties. Inoculation with F. mosseae or R. irregularis also conferred protection to the rice blast fungus, but the level of mycorrhiza-induced blast resistance varied among host genotypes. Rice seedlings (Loto and Gines varieties) were pre-inoculated with R. irregularis, transplanted into flooded fields, and grown until maturity. A significant increase in grain yield was observed in mycorrhizal plants compared with non-mycorrhizal plants, which was related to an increase in the number of panicles.

Conclusion
Results here presented support that rice plants benefit from the AM symbiosis while illustrating the potential of using AM fungi to improve productivity and blast resistance in cultivated rice. Differences observed in the mycorrhizal responsiveness among the different rice cultivars in terms of growth promotion and blast resistance indicate that evaluation of benefits received by the AM symbiosis needs to be carefully evaluated on a case-by-case basis for efficient exploitation of AM fungi in rice cultivation.
What is the response profile of deciduous pulp fibroblasts stimulated with E. coli LPS and E. faecalis LTA?
Authors: Colombini-Ishikiriama Bella Luna , Dionisio Thiago Jose , Garbieri Thais Francini , da Silva Rafaela Alves , Machado Maria Aparecida Andrade Moreira , de Oliveira Sandra Helena Penha , Lara Vanessa Soares , Greene Andrew Seth , Santos Carlos Ferreira 
Published: June 2020

Abstract
Background
Oral fibroblast immunological responses to bacterial stimuli are well known. However, there are few studies about pulp fibroblasts from deciduous teeth (HDPF) responses, which are important for the treatment of pulp infections in children. The aim of this study was to evaluate expression and production of inflammatory cytokines and chemokines by HDPF when challenged with bacterial antigens normally present in advanced caries lesions.

Methods
Triplicate HDPF from 4 children (n = 4; 2 boys and 2 girls) were cultured by explant technique and challenged or not with Escherichia coli lipopolysaccharide/1 μg/mL (EcLPS) or Enterococcus faecalis lipoteichoic acid/1 μg/mL (EfLTA) for 6 and 24 h. Most of published studies employed immortalized cells, i.e., without checking possible gender and genetic variables. mRNA expression and protein production were evaluated by RT-qPCR and ELISA MILLIPLEX®, respectively, for Interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, Chemokine C-C motif ligand 2/monocyte chemoattractant protein 1 (CCL2/MCP-1), Chemokine C-C motif ligand 3/macrophage inflammatory protein 1-alpha (CCL3/MIP1-α), Chemokine C-C motif ligand 5/ regulated on activation, normal T cell expressed and secreted (CCL5/RANTES), C-X-C motif chemokine 12/ stromal cell-derived factor 1 (CXCL12/SDF-1), Tumor Necrosis Factor-alpha (TNF-α), Interferon-gamma (IFN γ), Vascular Endothelial Growth Factor (VEGF), Colony stimulating factor 1 (CSF-1) and Macrophage colony-stimulating factor (M-CSF).

Results
EcLPS increased IL-1α, IL-1β, IL-8, CCL2, CCL5, TNF-α and CSF-1 mRNA and protein levels while EfLTA was only able to positively regulate gene expression and protein production of IL-8.

Conclusion
The results of the present study confirmed our hypothesis, since pulp fibroblasts from deciduous teeth are capable of increasing gene expression and protein production after being stimulated with EcLPS and EfLTA.
Practicalities in running early-phase trials using the time-to-event continual reassessment method (TiTE-CRM) for interventions with long toxicity periods using two radiotherapy oncology trials as examples
Authors: van Werkhoven Erik , Hinsley Samantha , Frangou Eleni , Holmes Jane , de Haan Rosemarie , Hawkins Maria , Brown Sarah , Love Sharon B 
Published: June 2020

Abstract
Background
Awareness of model-based designs for dose-finding studies such as the Continual Reassessment Method (CRM) is now becoming more commonplace amongst clinicians, statisticians and trial management staff. In some settings toxicities can occur a long time after treatment has finished, resulting in extremely long, interrupted, CRM design trials. The Time-to-Event CRM (TiTE-CRM), a modification to the original CRM, accounts for the timing of late-onset toxicities and results in shorter trial duration. In this article, we discuss how to design and deliver a trial using this method, from the grant application stage through to dissemination, using two radiotherapy trials as examples.

Methods
The TiTE-CRM encapsulates the dose-toxicity relationship with a statistical model. The model incorporates observed toxicities and uses a weight to account for the proportion of completed follow-up of participants without toxicity. This model uses all available data to determine the next participant’s dose and subsequently declare the maximum tolerated dose.
We focus on two trials designed by the authors to illustrate practical issues when designing, setting up, and running such studies.

Results
In setting up a TiTE-CRM trial, model parameters need to be defined and the time element involved might cause complications, therefore looking at operating characteristics through simulations is essential. At the grant application stage, we suggest resources to fund statisticians’ time before funding is awarded and make recommendations for the level of detail to include in funding applications. While running the trial, close contact of all involved staff is required as a dose decision is made each time a participant is recruited. We suggest ways of capturing data in a timely manner and give example code in R for design and delivery of the trial. Finally, we touch upon dissemination issues while the trial is running and upon completion.

Conclusion
Model-based designs can be complex. We hope this paper will help clinical trial teams to demystify the conduct of TiTE-CRM trials and be a starting point for using this methodology in practice.