bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of romiplostim immunogenicity in adult patients in clinical trials and in a global postmarketing registry
Authors: Mytych Daniel T. , Park Joseph K. , Kim June , Barger Troy E. , Boshier Andy , Jawa Vibha , Kuter David J. 
Published: April 2020

SummaryAntibodies to first‐generation recombinant thrombopoietin (TPO) neutralized endogenous TPO and caused thrombocytopenia in some healthy subjects and chemotherapy patients. The second‐generation TPO receptor agonist romiplostim, having no sequence homology to TPO, was developed to avoid immunogenicity. This analysis examined development of binding and neutralising antibodies to romiplostim or TPO among adults with immune thrombocytopenia (ITP) in 13 clinical trials and a global postmarketing registry. 60/961 (6·2%) patients from clinical trials developed anti‐romiplostim‐binding antibodies post‐baseline. The first positive binding antibody was detected 14 weeks (median) after starting romiplostim, at median romiplostim dose of 2 µg/kg and median platelet count of 29.5 × 109/l; most subjects had ≥98·5% of platelet assessments showing response. Neutralising antibodies to romiplostim developed in 0·4% of patients, but were unrelated to romiplostim dose and did not affect platelet count. Thirty‐three patients (3·4%) developed anti‐TPO‐binding antibodies; none developed anti‐TPO‐neutralising antibodies. In the global postmarketing registry, 9/184 (4·9%) patients with spontaneously submitted samples had binding antibodies. One patient with loss of response had anti‐romiplostim‐neutralising antibodies (negative at follow‐up). Collectively, anti‐romiplostim‐binding antibodies developed infrequently. In the few patients who developed neutralising antibodies to romiplostim, there was no cross‐reactivity with TPO and no associated loss of platelet response.
The declining place of music education in schools in England
Authors: Bath Naomi , Daubney Alison , Mackrill Duncan , Spruce Gary 
Published: April 2020

AbstractThis article addresses the provision of music education in schools in England, arguing that access to music education is the right of every child and therefore that a high‐quality and sustained curriculum offer must be provided in all state‐funded schools. Music education in England is widely recognised as being marginalised in state schools, despite it being a statutory requirement as part of the National Curriculum. This policy review examines several threats to music education, such as accountability measures, funding cuts, curriculum narrowing and erosion of the teaching workforce, identifying some of the key evidence in each case.
Down the up staircase: Equatorward march of a cold‐water ascidian and broader implications for invasion ecology
Authors: Chang Andrew L. , Carlton James T. , Brown Christopher W. , Ruiz Gregory M. 
Published: April 2020

AbstractAimWhile warming temperatures are expected to facilitate the poleward movement of species previously restricted to more equatorial waters, the arrival and persistence of cold‐water species in more equatorward waters are relatively unprecedented. The native north‐east Pacific ascidian Corella inflata Huntsman, 1912, has spread southward and invaded new regions along the North American Pacific coast, a rare example of a marine species moving towards the equator. Here, we document C. inflata's equatorward movement and potential impact, assess several hypotheses for its spread and consider implications for invasion ecology.LocationNorth American Pacific Coast (Puget Sound to San Francisco Bay).MethodsWe recorded the southward movement of C. inflata by compiling records from the literature, conducting informal searches and conducting standardized fouling community surveys at sites from the southern border of C. inflata's native range in Puget Sound to San Francisco Bay. Within San Francisco Bay, we recorded C. inflata's arrival and potential impact by conducting standardized surveys across an 18‐year period encompassing the invasion.ResultsFirst collected outside its native range in Coos Bay, Oregon, in 2004, C. inflata was subsequently detected 1,000 km south of its historical distribution by 2008 in San Francisco and Humboldt Bays, California. At times, this large, conspicuous solitary ascidian became locally abundant in San Francisco Bay fouling communities, which showed significant shifts in species composition and relative abundance at invaded sites concomitant with C. inflata's arrival.Main conclusionsThe recent southward movement of C. inflata runs counter to global warming expectations and may be linked to undetected changes in vessel traffic patterns, rather than natural range expansion. However, an understanding of the one or more processes that would serve to explain the equatorward movement of this cold‐water affinity marine species remains elusive.
Emerging Market Penetration and Emissions Performance
Authors: Wani Deepa , Dong Yan , Malhotra Manoj K. , Xu Kefeng 
Published: April 2020

ABSTRACTFirms move to emerging markets to sell their products, reach new markets, and to strategically offshore or outsource their production and supply chains. However, they may also take advantage of loose environmental regulations and weak protection of existing laws in emerging market countries. Anecdotal evidence and media reports claim that increased firm activity in emerging economies such as China, India, Brazil, among others, has resulted in more significant environmental pollution. However, statistical evidence is lacking in this area. This research consequently investigates the impact of two forms of emerging market presence: the extent of offshoring penetration and extent of sales penetration on emissions performance. We conduct an empirical study using a panel dataset consisting of 300 global firms across various industries, along with their emission levels and emerging market penetration levels. Analysis of over six years of data from 2007 to 2012 shows that even after factoring in the endogeneity related to entry into emerging markets, firms that have a greater degree of emerging market penetration do indeed have higher emissions. We also find that a firm's beneficial actions related to environmental corporate social performance attenuate the relationship between emerging market penetration and emissions, whereas a firm's harmful actions related to environmental corporate social performance amplifies this relationship. Implications of this study for a firm's future strategic location and offshoring decisions are discussed and presented.
Long‐term efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (the DEPICT‐2 study): 52‐week results from a randomized controlled trial
Authors: Mathieu Chantal , Rudofsky Gottfried , Phillip Moshe , Araki Eiichi , Lind Marcus , Arya Niki , Thorén Fredrik , Scheerer Markus F. , Iqbal Nayyar , Dandona Paresh 
Published: April 2020

AbstractAimTo investigate the long‐term efficacy and safety of dapagliflozin as an adjunct to adjustable insulin in adults with type 1 diabetes (T1D) and inadequate glycaemic control.Materials and MethodsDapagliflozin Evaluation in Patients with Inadequately Controlled Type 1 Diabetes (DEPICT‐2) was a placebo‐controlled, double‐blind, multicentre, phase III study of adults with T1D (HbA1c 7.5%‐10.5%) randomized (1:1:1) to receive dapagliflozin 5, 10 mg, or placebo. The efficacy and safety of dapagliflozin over 52 weeks were exploratory endpoints in this extension to DEPICT‐2.ResultsOf 813 participants randomized, 88.2% completed the study. From baseline to 52 weeks, dapagliflozin 5 and 10 mg were associated with reduction in HbA1c (difference [95% CI] vs. placebo: −0.20% [−0.34, −0.06] and −0.25% [−0.38, −0.11], respectively) and adjusted mean percentage change in body weight (difference [95% CI] vs. placebo: −4.42% [−5.19, −3.64] and −4.86% [−5.63, −4.08], respectively). Serious adverse events were reported in the dapagliflozin 5, 10 mg, and placebo groups (32 [11.8%], 19 [7.0%] and 16 [5.9%], respectively). The proportion of hypoglycaemic events was similar across groups; severe hypoglycaemia was uncommon. More participants with events adjudicated as definite diabetic ketoacidosis (DKA) were in the dapagliflozin 5 and 10 mg groups versus placebo (11 [4.1%], 10 [3.7%] and 1 [0.4%], respectively); the majority of events were mild or moderate in severity and all were resolved with treatment.ConclusionsDapagliflozin led to long‐term reductions in HbA1c and body weight in adults with T1D, but increased DKA risk compared with placebo.
The UK haemophilia specialist nurse: Competencies fit for practice in the 21st century
Authors: Pollard Debra , Harrison Catherine , Dodgson Sandra , Holland Mike , Khair Kate 
Published: April 2020

AbstractIntroductionNurses play a central co‐ordinating role in delivering comprehensive care for people with haemophilia and allied bleeding disorders, for which they need a broad range of competencies. The UK Haemophilia Nurses Association (HNA) published a role description in 1994 which was developed into a competency framework in 2014. This has now been updated to reflect current educational and clinical practice.AimTo summarize the evidence supporting the nurse's advanced role within haemophilia care and develop new competencies to deliver comprehensive care within a multidisciplinary team.MethodsSystematic reviews were identified by PubMed literature search. The HNA conducted workshops to consult its membership, and the authors incorporated this input to update its competency framework within the structure outlined by Health Education England in multiprofessional framework for advanced clinical practice in England (2017).ResultsThe proposed framework includes five domains (Clinical knowledge, Clinical/direct care, Communication and support, Collaborative practice and Research) supported by indicators for four levels of practice (beginner, competent, proficient and expert). The framework is a tool which nurses and their managers can use to assess skills and knowledge, and identify learning needs appropriate to personal development and improve patient care and outcomes.ConclusionThe HNA has developed a new competency framework to provide a strong foundation for haemophilia specialist nurses to continue improving services for people living with bleeding disorders and their families, as well as supporting personal development alongside new therapeutic options, models of care and follow‐up.
Comparative analysis of liver functional reserve during lenvatinib and sorafenib for advanced hepatocellular carcinoma
Authors: Terashima Takeshi , Yamashita Tatsuya , Takata Noboru , Toyama Tadashi , Shimakami Tetsuro , Takatori Hajime , Arai Kuniaki , Kawaguchi Kazunori , Kitamura Kazuya , Yamashita Taro , Sakai Yoshio , Mizukoshi Eishiro , Honda Masao , Kaneko Shuichi 
Published: April 2020

AimMost patients with advanced hepatocellular carcinoma (HCC) have underlying chronic liver disease, which potentially deteriorated the liver functional reserve that often affects the patients' clinical course. We investigated and compared the changes in liver functional reserve during lenvatinib or sorafenib therapy in patients with advanced HCC.MethodsWe prospectively collected medical information about patients with advanced HCC with a Child–Pugh score of 5–7 to compare the liver functional reserve during treatment in those who were treated with lenvatinib or sorafenib. We also evaluated the effect of the change in the liver functional reserve on patients' outcome. Moreover, we analyzed the contributing factors for maintaining the liver functional reserve during treatment.ResultsPatients were treated with lenvatinib (n = 45) or sorafenib (n = 157). Forty‐five patients in the lenvatinib group and 135 patients in the sorafenib group were selected through a propensity score matching analysis. More patients treated with lenvatinib had a Child–Pugh score that was maintained or improved after 4 and 12 weeks compared with those treated with sorafenib (P = 0.048, P = 0.036, respectively). Lenvatinib was identified as one of the variables that was associated with maintaining Child–Pugh scores. Multivariate analysis revealed that a worsened Child–Pugh score after 4 weeks was an independent unfavorable predictive factor for overall survival.ConclusionsMore patients treated with lenvatinib for advanced HCC maintained their liver functional reserves compared with those treated with sorafenib. Maintaining the liver functional reserve contributed to better outcomes for patients with advanced HCC.
Effect of synthetic microbial community on nutraceutical and sensory qualities of kombucha
Authors: Wang Shuai , Zhang Liming , Qi Libo , Liang Huipeng , Lin Xinping , Li Shengjie , Yu Chenxu , Ji Chaofan 
Published: April 2020

SummaryTo mass‐produce nutritional kombucha with quality consistency, it is necessary to design synthetic microbial community (SMC) starters with clear bacterial compositions. In this study, a three‐species SMC, including Acetobacter pasteurianus, Gluconacetobacter xylinus and Zygosaccharomyces bailii, was designed. Acetic acid bacteria (AAB) in SMC produced a higher concentration of organic acids synergistically compared to each strain inoculated alone. Gluconic acid was the most abundant organic acid in kombucha fermented by SMC, which contributed to the pleasant sour taste of the beverage. AAB could also oxidise the alcohol produced by Z. bailii, making kombucha a soft beverage. Total phenol and flavonoid concentrations increased during fermentation, which enhanced the health benefits of kombucha. The sensory evaluation demonstrated tsshat sensory attributes of SMC fermented kombucha were quite similar to those fermented by the symbiotic culture of bacteria and yeast (SCOBY). Therefore, SMC could be utilised in the industrial mass production of kombucha for better quality control and product consistency.
Characterisation of oleoresins extracted from tomato waste by liquid and supercritical carbon dioxide
Authors: Romano Raffaele , Aiello Alessandra , Pizzolongo Fabiana , Rispoli Andrea , De Luca Lucia , Masi Paolo 
Published: April 2020

AbstractTomato waste is characterised by high amounts of bioactive compounds, such as carotenoids, polyphenols and essential fatty acids. In this work, oleoresins were produced from tomato waste (skins + seeds) and skins using carbon dioxide under liquid and supercritical conditions. The use of ethanol as a co‐solvent was also evaluated. Compositions of the oleoresins were analysed and compared to oleoresin obtained by means of an organic solvent, which was used as the control. Oleoresin extraction from the waste by liquid and supercritical CO2 provided the highest yields (12.5%–12.9%). The extracts obtained from the skins with supercritical CO2 without ethanol had the highest content of α‐ and γ‐tocopherols (80 and 575 mg/100 g oleoresin, respectively), while lycopene and β‐carotene were found at 205 and 75 mg/100 g oleoresin, respectively. The highest quantity of polyphenols (9305 mg GAE/100 g oleoresin) was found in the oleoresin extracted from skin by supercritical CO2 with ethanol. All oleoresins were characterised by a high antioxidant activity, which improved with the synergy of carotenoids, tocopherols and polyphenols.
Development of a cancer-themed escape room learning activity for undergraduate pharmacy students
Authors: Wilby Kyle John , Kremer Lisa J 
Published: April 2020

Abstract

Objectives
The aim of this study was to evaluate the feasibility of a cancer-themed escape room as a learning activity for pharmacy students.

Methods
A cancer-themed escape room was developed with four activities linked to patient assessment, communication, therapeutics and calculations. Twenty-six groups of six students challenged the escape room. Outcomes included student performance measures and resources required. A SWOC (strengths, weaknesses, opportunities, and challenges) analysis was also conducted.

Results
A total of 20 student groups (77%) successfully escaped. The average escape time was 22 min. The SWOC analysis identified strengths of student engagement, opportunities for expansion, weaknesses related to student preparation, and some logistical challenges.

Conclusion
A cancer-themed escape room is a viable learning tool for pharmacy students.
Depletion of langerin+ cells enhances cutaneous wound healing
Authors: Rajesh Aarthi , Stuart Gabriella , Real Nicola , Ahn Jenny , Tschirley Allison , Wise Lyn , Hibma Merilyn 
Published: April 2020

SummaryLangerin is a C‐type lectin receptor that is expressed on Langerhans cells and langerin‐positive dermal dendritic cells in the skin. Little is known about the function of langerin+ cells in wound healing. In this study, the effects of ablation of langerin+ cells on healing of a full‐thickness excision wound were investigated using the langerin‐DTR depletable mouse. Strikingly, depletion of langerin+ cells resulted in more rapid reduction in wound area. Accelerated wound healing in the langerin+‐cell‐depleted group was characterized by enhanced neo‐epidermis and granulation tissue formation, and increased cellular proliferation within the newly formed tissues. Accelerated healing in the absence of langerin+ cells was associated with increased levels of granulocyte–macrophage colony‐stimulating factor, F4/80+ cells and blood vessels within the granulation tissue. These data support an inhibitory role for langerin+ cells during wound healing. Therapies that suppress langerin+ cells or their function may therefore have utility in progressing the healing of wounds in humans.
Drought priming effects on alleviating the photosynthetic limitations of wheat cultivars (Triticum aestivum L.) with contrasting tolerance to abiotic stresses
Authors: Mendanha Thayna , Rosenqvist Eva , Nordentoft Hyldgaard Benita , Doonan John H. , Ottosen Carl‐Otto 
Published: April 2020

AbstractAbiotic stress tolerance in plants is said to be induced by pre‐stress events (priming) during the vegetative phase. We aimed to test whether drought priming could improve the heat and drought tolerance in wheat cultivars. Two wheat cultivars “Gladius” and “Paragon” were grown in a fully controlled gravimetric platform and subjected to either no stress or two drought cycles during the tillering stage. At anthesis, both batches were either subjected to high temperature stress, drought stress or kept as control. No alleviation of grain yield reduction due to priming was observed. Higher CO2 assimilation rates were achieved due to priming under drought stress. Yield results showed that priming was not damage cumulative to wheat. Priming was responsible to alleviated biochemical photosynthetic limitations under drought stress and sustained photochemical utilization under heat stress in “Paragon.” Priming as a strategy in abiotic stress alleviation was better evidenced in the stress susceptible cultivar “Paragon” than tolerant cultivar “Gladius”; therefore, the type of response to priming appears to be cultivar dependable, and thus phenotypical variation should be expected when studying the effects of abiotic priming.
Limited contribution of water availability in genotype‐by‐environment interaction in sugarcane yield and yield components
Authors: Natarajan Sijesh , Basnayake Jaya , Lakshmanan Prakash , Fukai Shu 
Published: April 2020

AbstractWater deficit is an important abiotic stress factor limiting sugarcane production. Understanding the effect of water deficit on cane yield, yield components and genotype × environment (G × E) interaction can aid in selecting genotypes that are adapted to water deficit conditions. In this study, response of cane yield and yield components of 10 sugarcane genotypes grown under 3 irrigation treatments—fully irrigated, semi‐irrigated and rainfed—was examined across 3 locations and 3 crop‐years within each location. Cane yield reduced by 32% and 9% in the rainfed and semi‐irrigated treatments, respectively, compared to the fully irrigated treatment. Genotypic variation was highly significant for cane yield and yield components in all three irrigation regimes. Cane yield in the rainfed treatment showed significant genetic correlation with stalk diameter (rg = 0.68), leaf number (rg = 0.64), node number (rg = 0.67) and stalk number (rg = 0.68). Genotype × irrigation variance was negligible compared to genotype, genotype × location and genotype × crop‐year variances. Commercial genotypes had higher yield in most environments except in low‐yield potential environments, which caused a significant genotype × location × irrigation effect, suggesting opportunities for improving sugarcane productivity in these environments.
Exploring the nature and correlates of caregiving among parents of adults with intellectual and developmental disabilities
Authors: Burke Meghan M. , Rios Kristina , Aleman‐Tovar Janeth , Lee Chung eun , Arnold Catherine K. , Owen Aleksa 
Published: April 2020

AbstractBackgroundAs adults with intellectual and developmental disabilities (IDD) have longer lives, parents may remain caregivers into old age. In addition, it is unknown who will fulfil caregiving roles after parents are no longer able to be caregivers. In the current study, we explored the nature (e.g. number of hours of caregiving) and correlates of parental caregiving for their adult offspring with intellectual and developmental disabilities and their future caregiving plans.MethodIn the United States, data were collected from 334 parents of adults with intellectual and developmental disabilities via a national survey.ResultsAltogether, 55% of the sample spent more than 15 hr conducting caregiving per week. Individual characteristics (e.g. maladaptive behaviour and functional abilities) and parent characteristics (e.g. physical proximity of the adult with intellectual and developmental disabilities and caregiving ability) positively correlated with caregiving hours. Notably, 38.58% of participants were unsure who would fulfil caregiving roles.ConclusionImplications for research about caregiving and practice are discussed.
Molecular mechanisms involved in high glucose‐induced valve calcification in a 3D valve model with human valvular cells
Authors: Vadana Mihaela , Cecoltan Sergiu , Ciortan Letitia , Macarie Razvan D. , Tucureanu Monica M. , Mihaila Andreea C. , Droc Ionel , Butoi Elena , Manduteanu Ileana 
Published: April 2020

AbstractCalcific aortic valve disease (CAVD)—the most common valvular heart disease—is accelerated in diabetes and has no pharmacotherapy. Although it is known that early CAVD is associated with inflammation and osteogenesis, the molecular mechanisms involved in diabetes‐associated CAVD still need to be uncovered. In this context, we have developed a 3D construct based on gelatin populated with human valvular endothelial cells (VEC) and valvular interstitial cells (VIC) and evaluated the effect of high glucose (HG) concentration on osteogenic molecules expression and on calcification mechanisms. First, we characterized the 3D model and assessed VIC remodelling properties at different time‐points. Then, we exposed it to normal glucose (NG) or high glucose (HG) for 7, 14 and 21 days after which the cells were isolated, separated and investigated individually. Our results showed that encapsulated VIC actively remodel the hydrogel, as demonstrated by an increased expression of extracellular matrix (ECM) proteins and matrix metalloproteinases (MMPs). Moreover, exposure of the construct to HG triggered bone morphogenetic protein (BMP) and TGF‐β signalling pathways, up‐regulating expression of osteogenic molecules—BMP‐2/‐4, osteocalcin, osteopontin, SMADs and Runt‐related transcription factor (Runx‐2)—and increased calcium deposits in an osteogenic environment. These findings underline the potential of the developed 3D model as a suitable system to investigate the mechanisms of human CAVD and may help to better understand the calcification mechanisms in CAVD associated to diabetes.