bluuebunny/crossref_metadata_2025_split huggingface dataset:
Facilitators and barriers to advance care planning implementation in Australian aged care settings: A systematic review and thematic analysis
Authors: Batchelor Frances , Hwang Kerry , Haralambous Betty , Fearn Marcia , Mackell Paulene , Nolte Linda , Detering Karen 
Published: March 2019

ObjectivesThere are many studies investigating implementation of advance care planning (ACP) in aged care around the world, but few studies have investigated Australian settings. The objective of this study was to determine facilitators and barriers to implementation of ACP in Australian residential and community aged care.MethodsEvidence from Australian studies published between 2007 and September 2017 of ACP in residential and community aged care was sourced from electronic databases using predetermined search strategies. Data were extracted and synthesised using thematic analysis, and summarised according to themes.ResultsNine studies described facilitators and barriers of ACP implementation. Six themes were identified: “Education and Knowledge,” “Skills and Training,” “Procedures and Resources,” “Perceptions and Culture,” “Legislation” and “Systems.”ConclusionsA whole of systems approach is necessary to facilitate uptake of ACP in residential aged care settings. More research is needed to understand facilitators and barriers to ACP in community aged care.
A multicenter observational study of the real‐world use of docetaxel for metastatic castration‐resistant prostate cancer in China
Authors: He Dalin , Sun Zhongquan , Guo Jianming , Zhang Zhigen , Shan Yuxi , Ma Lulin , Li Hanzhong , Jin Jie , Huang Yiran , Xiao Jiaquan , Wei Qiang , Ye Dingwei 
Published: March 2019

AbstractAimTo investigate the use of docetaxel for the treatment of metastatic castration‐resistant prostate cancer (mCRPC) in real‐world clinical practice in China.MethodsThis single‐arm, prospective, observational study was conducted at 32 study centers in China and included male patients aged ≥18 years with histologically confirmed prostate cancer who received ≥1 dose of docetaxel following failure of hormonal therapy (disease progression with serum testosterone <50 ng/dL). The primary aim was to investigate patterns of docetaxel treatment.ResultsOverall 403 patients were included between August 2011 and June 2016; patients initiated docetaxel after failure of first‐ (42.2% [170]), second‐ (31.0% [125]) and ≥third‐line (12.7% [51]) hormonal therapy, estramustine (11.4% [46]) or other (2.7% [11]). The planned cycles of docetaxel therapy were completed by 30.8% of patients, and the mean (SD) number of cycles received was 4.4 (2.86). Median overall survival (mOS) was 22.4 (95% CI, 20.4–25.8) months and the prostate‐specific antigen (PSA) response rate in patients with available data was 70.9% (168/237), with no differences in mOS and PSA response rates between treatment settings. Subgroup analysis revealed higher mOS in patients without visceral metastasis versus those with such metastases (22.9 vs. 17.4 months; P = 0.022). No new safety signals were observed and the most common adverse events associated with docetaxel were granulocytopenia (5%) and leukopenia (4.5%).ConclusionData from this study showed that around three‐quarters of Chinese patients with mCRPC treated with docetaxel initiated treatment following first‐ or second‐line hormonal therapy and no new safety signals were observed.
The efficacy and safety of glecaprevir plus pibrentasvir in 141 patients with severe renal impairment: a prospective, multicenter study
Authors: Atsukawa Masanori , Tsubota Akihito , Toyoda Hidenori , Takaguchi Koichi , Nakamuta Makoto , Watanabe Tsunamasa , Michitaka Kojiro , Ikegami Tadashi , Nozaki Akito , Uojima Haruki , Fukunishi Shinya , Genda Takuya , Abe Hiroshi , Hotta Naoki , Tsuji Kunihiko , Ogawa Chikara , Tachi Yoshihiko , Shima Toshihide , Shimada Noritomo , Kondo Chisa , Akahane Takehiro , Aizawa Yoshio , Tanaka Yasuhito , Kumada Takashi , Iwakiri Katsuhiko 
Published: March 2019

SummaryBackgroundPatients with chronic hepatitis C are often complicated by chronic kidney disease (CKD).AimTo evaluate the efficacy, safety and pharmacokinetics of glecaprevir/pibrentasvir in patients with severe renal impairment.MethodsIn a prospective, multicentre study involving 35 medical institutions, 832 genotype 1‐3 patients were treated with glecaprevir/pibrentasvir. The efficacy and safety of glecaprevir/pibrentasvir were analysed for patients with CKD stage 4 or 5. Multivariate analysis was performed to identify the factors associated with the most frequently observed adverse event. In patients undergoing haemodialysis, a pharmacokinetic study was conducted to investigate the dialysability of the drugs: plasma samples were obtained from the arterial and venous sides of a dialyser to serially measure drug concentrations.ResultsThe subjects comprised 141 patients (32 with CKD stage 4 and 109 with CKD stage 5), of whom 100 were undergoing haemodialysis. All but one stage 5 CKD patients undergoing haemodialysis achieved sustained virologic response (99.3%). Adverse events were observed in 39.7% of subjects: pruritus was the most frequent (30.5%), and was significantly associated with haemodialysis. In the pharmacokinetic study, no arterial‐venous differences in the plasma concentrations of glecaprevir/pibrentasvir were detected during the haemodialysis sessions.ConclusionsGlecaprevir/pibrentasvir was highly effective and safe in chronic hepatitis C patients with severe renal impairment. Haemodialysis was associated with increased incidence of pruritus, which was the most frequent adverse event, but had little or no influence on the drug concentrations, which indicated that their dialysability is very low and that no dose modification is required in patients undergoing haemodialysis. (UMIN registration no. 000032073).
Checking the pregnancy checkbox: Evaluation of a four‐state quality assurance pilot
Authors: Daymude Anna E. C. , Catalano Andrea , Goodman Dave 
Published: March 2019

AbstractBackgroundThe 2003 revision of the standard United States death certificate included a set of “pregnancy checkboxes” to ascertain whether a woman was pregnant at the time of her death or within the preceding year. Studies validating the pregnancy checkbox have indicated a potentially high number of errors, resulting in inflated maternal mortality rates. In response to concerns about pregnancy checkbox data quality, four state health departments implemented a quality assurance pilot project examining the accuracy of the pregnancy checkbox for 2016 deaths.MethodsState staff conducted searches for birth or fetal death reports that matched a death certificate, within a year of death. If a pregnancy checkbox was marked, but no match was found between certificates, confirmation of the pregnancy was attempted through active follow‐up with the death certifier. From December 2017 to January 2018, the quality assurance pilot was evaluated through three focus groups with key stakeholders. The evaluation aimed to describe opportunities and challenges to implementation, sustainability, and lessons learned.ResultsOpportunities for implementing the pilot included written documentation of the quality assurance process, improved certifier response, improved data quality, and increased data timeliness for Maternal Mortality Review Committees. Challenges included initial delays in certifier response, staff turnover, high caseloads in relation to resources, and lack of pilot prioritization in the health department. All four pilot states plan to sustain the pregnancy checkbox quality assurance process in some capacity.ConclusionsImplementing quality assurance processes for the pregnancy checkbox may ultimately improve state and national maternal death data quality.
Flipped learning and parent engagement in secondary schools: A South Australian case study
Authors: Bond Melissa 
Published: March 2019

AbstractParent involvement in and engagement with children’s learning has been shown to strongly influence student achievement, engagement, motivation and school completion. However, parent involvement decreases once students reach middle school, as subject content gets harder, the number of teachers increases, and students are less likely to share their homework and learning with parents. To this end, the flipped learning (FL) approach has received growing attention, with evidence of improved higher order thinking and collaborative skills and increased transparency for parents. This paper explores school leader, parent, student and teacher perceptions of the FL approach, through the lens of a 1‐year case study of two rural South Australian schools, in order to uncover how the approach affects parent engagement. Findings reveal that, whilst stakeholders feel that the flipped approach is beneficial for absent students, to reinforce content and increase student responsibility, it has not yet improved transparency for parents, with a disconnect between what schools think parents know and are engaging in, and the actual level of parent engagement in student learning. Recommendations for schools implementing the FL approach are provided against a bioecological model, adapted for this study.
Where is the “theory” within the field of educational technology research?
Authors: Hew Khe Foon , Lan Min , Tang Ying , Jia Chengyuan , Lo Chung Kwan 
Published: March 2019

AbstractCritics often characterise the study of educational technology as under‐theorised. To test this assertion and to determine the extent of this criticism, the present paper reports an in‐depth analysis of the 503 most recent empirical articles published in three selected education‐technology‐related journals (Computers & Education; Learning, Media and Technology; and British Journal of Educational Technology). These journals were selected because they publish studies related to all education settings rather than focusing on only a certain segment such as higher education; they have broad geographical catchment; and they were the most highly ranked journals in terms of their 2017 journal citation impact factor. The present paper examines how explicitly existing theory was identified in previous research, how theories were applied and how often these theories were advanced in education technology research. In the majority of cases, explicit engagement with theory was absent. Many studies either were wholly bereft of theories or made vague use of theory. Where theory was explicit, the articles were more likely to use theory to conceptualise the research, to inform the data collection or analysis process and to discuss the results. Very few articles reported findings that help us to learn something new about a particular theory (ie, little evidence of theory advancement).
Expression and function of phosphoinositide 3‐kinase delta in mesenchymal stromal cells from normal and leukaemic bone marrow
Authors: Ali Ahmed Y. , Guan Qingdong , Wu Xun , Hou Sen , Banerji Versha , Johnston James B. , Wall Donna , Szwajcer David , Gibson Spencer B. , Marshall Aaron J. 
Published: March 2019

SummaryWithin lymphoid tissues, chronic lymphocytic leukaemia (CLL) cells interact with mesenchymal stromal cells (MSC). Inhibitors of phosphoinositide 3‐kinase delta (PI3Kδ) cause release of CLL cells from lymphoid tissues into blood. PI3Kδ inhibitors are thought to target only CLL and other immune cells because PI3Kδ expression is restricted to haematopoietic cells. We found that PI3Kδ is unexpectedly expressed in primary MSC derived from CLL patients and healthy donors. PI3Kδ inhibition in MSC using idelalisib or duvelisib significantly reduced their ability to support CLL migration and adhesion. These observations provide the first evidence that PI3Kδ is expressed and functional in CLL MSC.
CD4+CD25−LAG3+ regulatory T cells in humoral immunity
Authors: Inoue Mariko , Okamura Tomohisa , Komai Toshihiko , Yamamoto Kazuhiko , Fujio Keishi 
Published: March 2019

AbstractRegulatory T cells (Tregs) are necessary for the maintenance of peripheral immune tolerance. These Tregs are divided into two main subsets: thymus‐derived Tregs and peripherally‐derived Tregs. As a thymus‐derived Treg subset, CD4+CD25+ Tregs (CD25+ Tregs) that express the transcription factor, Forkhead box P3 (Foxp3), have been extensively studied. Type 1 regulatory T cells are representative Foxp3‐independent peripherally‐derived Tregs that produce a large amount of the inhibitory cytokine, interleukin (IL)‐10, and suppress immune responses through IL‐10 production. Accumulating evidence has shown that lymphocyte activation gene 3 (LAG3) is a reliable cell surface marker for type 1 regulatory T cells. Peripherally‐derived CD4+CD25−LAG3+ Tregs (LAG3+ Tregs) produce a large amount of IL‐10 and suppress colitis in a mouse model in an IL‐10‐dependent manner. LAG3+ Tregs characteristically express transcriptional factor early growth response gene 2 (Egr2), and ectopic expression of Egr2 conferred a suppressive function to CD4+ T cells. Intriguingly, polymorphism of the EGR2 gene is associated with susceptibility to systemic lupus erythematosus characterized by a wide spectrum of auto‐antibodies, and mice lacking Egr2 specifically in lymphocytes develop a lupus‐like autoimmune disease. We recently reported that Egr2‐expressing LAG3+ Tregs effectively suppress humoral immune responses in a transforming growth factor β3‐dependent manner. In addition, transforming growth factor β3 and IL‐10 synergistically regulate Toll‐like receptor‐mediated humoral immune responses. In the present review, we focus on the role of LAG3+ Tregs in humoral immunity, and also discuss its therapeutic potential for the treatment of autoimmune diseases.
Obesity paradox in cancer: Is bigger really better?
Authors: Ujvari Beata , Jacqueline Camille , Misse Dorothée , Amar Valentin , Fitzpatrick Jay C. , Jennings Geordie , Beckmann Christa , Rome Sophie , Biro Peter A. , Gatenby Robert , Brown Joel , Almeida Luis , Thomas Frédéric 
Published: March 2019

AbstractWhile obesity is widely recognized as a risk factor for cancer, survival among patients with cancer is often higher for obese than for lean individuals. Several hypotheses have been proposed to explain this “obesity paradox,” but no consensus has yet emerged. Here, we propose a novel hypothesis to add to this emerging debate which suggests that lean healthy persons present conditions unfavorable to malignant transformation, due to powerful natural defenses, whereby only rare but aggressive neoplasms can emerge and develop. In contrast, obese persons present more favorable conditions for malignant transformation, because of several weight‐associated factors and less efficient natural defenses, leading to a larger quantity of neoplasms comprising both nonaggressive and aggressive ones to regularly emerge and progress. If our hypothesis is correct, testing would require the consideration of the raw quantity, not the relative frequency, of aggressive cancers in obese patients compared with lean ones. We also discuss the possibility that in obese persons, nonaggressive malignancies may prevent the subsequent progression of aggressive cancers through negative competitive interactions between tumors.
Global advanced bioenergy potential under environmental protection policies and societal transformation measures
Authors: Wu Wenchao , Hasegawa Tomoko , Ohashi Haruka , Hanasaki Naota , Liu Jingyu , Matsui Tetsuya , Fujimori Shinichiro , Masui Toshihiko , Takahashi Kiyoshi 
Published: March 2019

AbstractBioenergy plays an important role in low greenhouse gas stabilization scenarios. Among various possible sources of bioenergy, dedicated bio‐crops could contribute to most of the potential. However, large scale bio‐crop deployment raises sustainability concerns. Policies to alleviate the pressure of bio‐crops on the terrestrial environment can affect bioenergy potential and production costs. Here, we estimated the maximum bioenergy potential under environmental protection policies (biodiversity and soil protection) and societal transformation measures from demand and supply side (demand‐side policy includes sustainable diet; supply‐side policy includes advanced technology and trade openness for food) by using an integrated assessment modelling framework, which consists of a general equilibrium model (Asian‐Pacific Integrated Model/Computable General Equilibrium) and a spatial land use allocation model (Asian‐Pacific Integrated Model/Platform for Land‐Use and Environmental Model). We found that the global advanced bioenergy potential under no policy was 245 EJ/year and that 192 EJ/year could be produced under US$5/GJ. These figures were 149 EJ/year and 110 EJ/year, respectively, under a full environmental policy. Biodiversity protection has a greater impact than soil protection due to its larger coverage and stronger implementation. Societal transformation measures effectively increase them to 186 EJ/year and 143 EJ/year, respectively, even under full environmental policies. These results imply that the large‐scale bioenergy deployment possibly needed for the climate target to limit the global mean temperature increase well below 2°C compared to the preindustrial level might face a trade‐off with environmental protection targets and that possible mitigation pathways in harmony with other environmental issues need to be explored.
Level of agreement between frequently used cardiovascular risk calculators in people living with HIV
Authors: Dhillon S , Sabin CA , Alagaratnam J , Bagkeris E , Post FA , Boffito M , Anderson J , Vera J , Williams I , Johnson M , Sachikonye M , Babalis D , Mallon PW , Winston A ,   the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) study
Published: March 2019

ObjectivesThe aim of the study was to describe agreement between the QRISK2, Framingham and Data Collection on Adverse Events of Anti‐HIV Drugs (D:A:D) cardiovascular disease (CVD) risk calculators in a large UK study of people living with HIV (PLWH).MethodsPLWH enrolled in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) study without a prior CVD event were included in this study. QRISK2, Framingham CVD and the full and reduced D:A:D CVD scores were calculated; participants were stratified into ‘low’ (< 10%), ‘intermediate’ (10–20%) and ‘high’ (> 20%) categories for each. Agreement between scores was assessed using weighted kappas and Bland–Altman plots.ResultsThe 730 included participants were predominantly male (636; 87.1%) and of white ethnicity (645; 88.5%), with a median age of 53 [interquartile range (IQR) 49–59] years. The median calculated 10‐year CVD risk was 11.9% (IQR 6.8–18.4%), 8.9% (IQR 4.6–15.0%), 8.5% (IQR 4.8–14.6%) and 6.9% (IQR 4.1–11.1%) when using the Framingham, QRISK2, and full and reduced D:A:D scores, respectively. Agreement between the different scores was generally moderate, with the highest level of agreement being between the Framingham and QRISK2 scores (weighted kappa = 0.65) but with most other kappa coefficients in the 0.50–0.60 range.ConclusionsEstimates of predicted 10‐year CVD risk obtained with commonly used CVD risk prediction tools demonstrate, in general, only moderate agreement among PLWH in the UK. While further validation with clinical endpoints is required, our findings suggest that care should be taken when interpreting any score alone.
The Healthy Homes/Healthy Kids 5‐10 Obesity Prevention Trial: 12 and 24‐month outcomes
Authors: Sherwood Nancy E. , Levy Rona L. , Seburg Elisabeth M. , Crain A. Lauren , Langer Shelby L. , JaKa Meghan M. , Kunin‐Batson Alicia , Jeffery Robert W. 
Published: March 2019

SummaryBackgroundPediatric primary care is an important setting for addressing obesity prevention.ObjectiveThe Healthy Homes/Healthy Kids 5‐10 randomized controlled trial evaluated the efficacy of an obesity prevention intervention integrating pediatric primary care provider counseling and parent‐targeted phone coaching.MethodsChildren aged 5 to 10 years with a BMI between the 70th and 95th percentile and their parents were recruited from pediatric primary care clinics. Participants received well‐child visit provider counseling about obesity and safety/injury prevention and were then randomized to a 14‐session phone‐based obesity prevention (OP; n = 212) or safety and injury prevention contact control (CC; n = 209) intervention. The primary outcome was 12 and 24‐month child BMI percentile.ResultsThere was no overall significant treatment effect on child BMI percentile. Caloric intake was significantly lower among OP compared with CC participants at 12 months (P < .005). In planned subgroup analyses, OP condition girls had significantly lower BMI percentile (P < .05) and BMI z‐score (P < .02) at 12 and 24 months relative to CC girls and were less likely to be overweight (38.0% vs 53.0%, P < .01) or (obese 3.4% vs 8.8%, P < .10) at follow‐up.Conclusions and RelevanceAn obesity prevention intervention integrating brief provider counseling and parent‐targeted phone counseling did not impact 12 and 24‐month BMI status overall but did have a significant impact on BMI in girls.
Plasma cells: You are what you eat
Authors: D'Souza Lucas , Bhattacharya Deepta 
Published: March 2019

SummaryPlasma cells are terminally differentiated B lymphocytes that constitutively secrete antibodies. These antibodies can provide protection against pathogens, and their quantity and quality are the best clinical correlates of vaccine efficacy. As such, plasma cell lifespan is the primary determinant of the duration of humoral immunity. Yet dysregulation of plasma cell function can cause autoimmunity or multiple myeloma. The longevity of plasma cells is primarily dictated by nutrient uptake and non‐transcriptionally regulated metabolic pathways. We have previously shown a positive effect of glucose uptake and catabolism on plasma cell longevity and function. In this review, we discuss these findings with an emphasis on nutrient uptake and its effects on respiratory capacity, lifespan, endoplasmic reticulum stress, and antibody secretion in plasma cells. We further discuss how some of these pathways may be dysregulated in multiple myeloma, potentially providing new therapeutic targets. Finally, we speculate on the connection between plasma cell intrinsic metabolism and systemic changes in nutrient availability and metabolic diseases.
T follicular helper cell heterogeneity: Time, space, and function
Authors: Song Wenzhi , Craft Joe 
Published: March 2019

SummaryT follicular helper (Tfh) cells play a crucial role in orchestrating the humoral arm of adaptive immune responses. Mature Tfh cells localize to follicles in secondary lymphoid organs (SLOs) where they provide help to B cells in germinal centers (GCs) to facilitate immunoglobulin affinity maturation, class‐switch recombination, and generation of long‐lived plasma cells and memory B cells. Beyond the canonical GC Tfh cells, it has been increasingly appreciated that the Tfh phenotype is highly diverse and dynamic. As naive CD4+ T cells progressively differentiate into Tfh cells, they migrate through a variety of microanatomical locations to obtain signals from other cell types, which in turn alters their phenotypic and functional profiles. We herein review the heterogeneity of Tfh cells marked by the dynamic phenotypic changes accompanying their developmental program. Focusing on the various locations where Tfh and Tfh‐like cells are found, we highlight their diverse states of differentiation. Recognition of Tfh cell heterogeneity has important implications for understanding the nature of T helper cell identity specification, especially the plasticity of the Tfh cells and their ontogeny as related to conventional T helper subsets.