bluuebunny/crossref_metadata_2025_split huggingface dataset:
How pragmatic are the randomised trials used in recommendations for control of glycosylated haemoglobin levels in type 2 diabetic patients in general practice: an application of the PRECIS II tool
Authors: Ettori-Ajasse Isabelle , Tatin Elise , Forbes Gordon , Eldridge Sandra , Dibao-Dina Clarisse 
Published: March 2020

Abstract
Background
Recommendations for good clinical practice have been reported to be difficult to apply in real life by primary care clinicians. This could be because the clinical trials at the origin of the guidelines are based on explanatory trials, conducted under ideal conditions not reflecting the reality of primary care, rather than pragmatic trials conducted under real-life conditions. The objective of this study was to evaluate how pragmatic are the clinical trials used to build the French High Authority of Health’s recommendations on the management of type II diabetes.

Methods
Trials from the 2013 Cochrane meta-analysis that led to the 2013 French High Authority of Health’s recommendations on the management of type II diabetes were selected. Each trial was analysed by applying the PRECIS-2 tool to evaluate whether the trial was pragmatic or explanatory, according to the nine domains of PRECIS-2. Each domain was scored between 1 (very explanatory) and 5 (very pragmatic) by two blinded researchers, and consensus was reached with a third researcher in case of discrepancy. Median scores were calculated for each of the nine domains.

Results
Twenty-three articles were analysed. Eight out of nine domains – namely eligibility, recruitment, setting, organisation, flexibility of delivery, flexibility of adherence, follow-up, and primary outcome – had a median score of less than 3, indicating a more explanatory design. Only the primary analysis domain had a score indicating a more pragmatic approach (median score of 4). In more than 25% of the articles, data to score the domains of recruitment, flexibility of delivery, flexibility of adherence, and primary analysis were missing.

Conclusions
Trials used to build French recommendations for good clinical practice for the management of type 2 diabetes in primary care were more explanatory than pragmatic. Policy-makers should encourage the funding of pragmatic trials to evaluate the different strategies proposed for managing the patient’s treatment according to HbA1C levels and give clinicians feasible recommendations.
Cis-regulatory analysis of Onecut1 expression in fate-restricted retinal progenitor cells
Authors: Patoori Sruti , Jean-Charles Nathalie , Gopal Ariana , Sulaiman Sacha , Gopal Sneha , Wang Brian , Souferi Benjamin , Emerson Mark M. 
Published: March 2020

Abstract
Background
The vertebrate retina consists of six major classes of neuronal cells. During development, these cells are generated from a pool of multipotent retinal progenitor cells (RPCs) that express the gene Vsx2. Fate-restricted RPCs have recently been identified, with limited mitotic potential and cell fate possibilities compared to multipotent RPCs. One population of fate-restricted RPCs, marked by activity of the regulatory element ThrbCRM1, gives rise to both cone photoreceptors and horizontal cells. These cells do not express Vsx2, but co-express the transcription factors (TFs) Onecut1 and Otx2, which bind to ThrbCRM1. The components of the gene regulatory networks that control the transition from multipotent to fate-restricted gene expression are not known. This work aims to identify and evaluate cis-regulatory elements proximal to Onecut1 to identify the gene regulatory networks involved in RPC fate-restriction.

Method
We identified regulatory elements through ATAC-seq and conservation, followed by reporter assays to screen for activity based on temporal and spatial criteria. The regulatory elements of interest were subject to deletion and mutation analysis to identify functional sequences and evaluated by quantitative flow cytometry assays. Finally, we combined the enhancer::reporter assays with candidate TF overexpression to evaluate the relationship between the TFs, the enhancers, and early vertebrate retinal development. Statistical tests included ANOVA, Kruskal-Wallis, or unpaired t-tests.

Results
Two regulatory elements, ECR9 and ECR65, were identified to be active in ThrbCRM1(+) restricted RPCs. Candidate bHLH binding sites were identified as critical sequences in both elements. Overexpression of candidate bHLH TFs revealed specific enhancer-bHLH interactions. Nhlh1 overexpression expanded ECR65 activity into the Vsx2(+) RPC population, and overexpression of NeuroD1/NeuroG2/NeuroD4 had a similar effect on ECR9. Furthermore, bHLHs that were able to activate ectopic ECR9 reporter were able to induce endogenous Otx2 expression.

Conclusions
This work reports a large-scale screen to identify spatiotemporally specific regulatory elements near the Onecut1 locus. These elements were used to identify distinct populations in the developing retina. In addition, fate-restricted regulatory elements responded differentially to bHLH factors, and suggest a role for retinal bHLHs upstream of the Otx2 and Onecut1 genes during the formation of restricted RPCs from multipotent RPCs.
Heteroexpression of Osa-miR319b improved switchgrass biomass yield and feedstock quality by repression of PvPCF5
Authors: Liu Yanrong , Yan Jianping , Wang Kexin , Li Dayong , Han Yejun , Zhang Wanjun 
Published: March 2020

Abstract
Background
Switchgrass (Panicum virgatum L.), a C4 perennial grass, has been recognized as one of the most potentially important lignocellulose biofuel crops. MicroRNA319 (miR319) plays a key role in plant development, abiotic resistance, and cell wall biosynthesis by repressing expression of its target TCP genes. We hypothesized miR319–TCP pathway could play important roles in switchgrass feedstock characteristics for biofuel production, and produced switchgrass transgenic plants overexpressing miR319 (by ectopic expressing Osa-MIR319b gene), blocking miR319 (by overexpressing a target mimicry of miR319/MIM319) and repression of miR319 target gene PvPCF5. Plant phenotype, biomass yield, and feedstock quality of transgenic plants were analyzed.

Results
Overexpression of miR319 in switchgrass promoted leaf elongation and expansion of transgenic plants, increased plant height, stem diameter, and resulted in a significant increase in plant biomass yield. Transgenic plants overexpressing of miR319 reduced lignin content, showed significantly higher enzymatic hydrolysis efficiency compared to the wild type plant. However, opposite results were observed in the MIM319 plants. Furthermore, suppression of miR319 target gene PvPCF5 activity also reduced lignin content, increased lignin monomer S/G ratio and the proportion of β-O-4 linkages, while significantly improving the sugar production per plant. Quantitative real-time (qRT-PCR) analysis indicated that expression of PvMYB58/63B and PvHCT with predicted TCP binding sites in their promoter regions was negatively regulated by miR319–PvPCF5 module.

Conclusions
MiR319–PvPCF5 module plays positive roles in regulating biomass yield and quality of switchgrass. It can be utilized as a candidate molecular tool in regulating biomass yield and feedstock quality. The finding could also be transferred to other grasses for forage quality improvement through genetic manipulation.
Oncomelania hupensis retains its ability to transmit Schistosoma japonicum 13 years after migration from permissive to non-permissive areas
Authors: Sun Cheng-song , Luo Fang , Liu Xin , Miao Feng , Hu Wei 
Published: March 2020

Abstract
Background
The East Route Project (ERP) of the South-to-North Water Diversion Project (SNWDP) stretches across schistosomiasis endemic and non-endemic areas in China, which may lead to the dispersal of Oncomelania hupensis, the intermediate host of Schistosoma japonicum, from permissive areas along the Yangtze River Basin to non-permissive areas in northern China. A previous survey demonstrated that O. hupensis could survive and breed for 13 years (12 generations) after being transferred to a non-permissive area, and could be infected by S. japonicum. However, it is not clear if the migrated snails will change their ability to transmit S. japonicum.

Methods
We infected mice with the cercariae released from the infected transferred snails bred in Jining city of Shandong Province (non-permissive areas) for 13 years. The mice in the control group were infected with cercariae derived from the snails collected in their original habitat (Jiangdu county of Jiangsu Province, permissive areas). Then, we explored the pathogenicity to mice including worm burden, liver egg count and pathology. Additionally, the gene expression profiles of the adult male and female worms recovered from the infected mice were analyzed by RNA sequencing.

Results
The worm burden, liver egg count and pathology of the mice infected with cercariae released from transferred snails bred in non-permissive areas for 13 years showed no significant differences, when compared with the control cercariae. Slight changes occurred at the transcription level between adult male and female worms recovered from mice infected with cercariae derived from snails bred in permissive and non-permissive areas. Only fourteen genes were significantly differentially expressed in the comparison of adult female worms, and no significantly differentially expressed gene was found in the comparison of adult male worms.

Conclusions
Our findings strongly suggest that transferred snails did not change their schistosomiasis transmission ability and the worms derived from them retained the original pathogenicity, even after migrating from permissive to non-permissive areas for 13 years. Therefore, a long-term surveillance system of snails along the SNWDP is urgently needed to prevent the diffusion of O. hupensis and reduce the risk of transmission of schistosomiasis.
Tracking cancer progression: from circulating tumor cells to metastasis
Authors: Castro-Giner Francesc , Aceto Nicola 
Published: March 2020

AbstractThe analysis of circulating tumor cells (CTCs) is an outstanding tool to provide insights into the biology of metastatic cancers, to monitor disease progression and with potential for use in liquid biopsy-based personalized cancer treatment. These goals are ambitious, yet recent studies are already allowing a sharper understanding of the strengths, challenges, and opportunities provided by liquid biopsy approaches. For instance, through single-cell-resolution genomics and transcriptomics, it is becoming increasingly clear that CTCs are heterogeneous at multiple levels and that only a fraction of them is capable of initiating metastasis. It also appears that CTCs adopt multiple ways to enhance their metastatic potential, including homotypic clustering and heterotypic interactions with immune and stromal cells. On the clinical side, both CTC enumeration and molecular analysis may provide new means to monitor cancer progression and to take individualized treatment decisions, but their use for early cancer detection appears to be challenging compared to that of other tumor derivatives such as circulating tumor DNA. In this review, we summarize current data on CTC biology and CTC-based clinical applications that are likely to impact our understanding of the metastatic process and to influence the clinical management of patients with metastatic cancer, including new prospects that may favor the implementation of precision medicine.
A Canadian evaluation framework for quality improvement in childhood arthritis: key performance indicators of the process of care
Authors: Barber Claire E. H. , Twilt Marinka , Pham Tram , Currie Gillian R. , Benseler Susanne , Yeung Rae S. M. , Batthish Michelle , Blanchette Nicholas , Guzman Jaime , Lang Bianca , LeBlanc Claire , Levy Deborah M. , O’Brien Christine , Schmeling Heinrike , Soon Gordon , Spiegel Lynn , Whitney Kristi , Marshall Deborah A. 
Published: March 2020

Abstract
Background
The evaluation of quality of care in juvenile idiopathic arthritis (JIA) is critical for advancing patient outcomes but is not currently part of routine care across all centers in Canada. The study objective is to review the current landscape of JIA quality measures and use expert panel consensus to define key performance indicators (KPIs) that are important and feasible to collect for routine monitoring in JIA care in Canada.

Methods
Thirty-seven candidate KPIs identified from a systematic review were reviewed for inclusion by a working group including 3 pediatric rheumatologists. A shortlist of 14 KPIs was then assessed using a 3-round modified Delphi panel based on the RAND/UCLA Appropriateness Method. Ten panelists across Canada participated based on their expertise in JIA, quality measurement, or lived experience as a parent of a child with JIA. During rounds 1 and 3, panelists rated each KPI on a 1–9 Likert scale on themes of importance, feasibility, and priority. In round 2, panelists participated in a moderated in-person discussion that resulted in minor modifications to some KPIs. KPIs with median scores of ≥ 7 on all 3 questions without disagreement were included in the framework.

Results
Ten KPIs met the criteria for inclusion after round 3. Five KPIs addressed patient assessments: pain, joint count, functional status, global assessment of disease activity, and the clinical Juvenile Arthritis Disease Activity Score (cJADAS). Three KPIs examined access to care: wait times for consultation, access to pediatric rheumatologists within 1 year of diagnosis, and frequency of clinical follow-up. Safety was addressed through KPIs on tuberculous screening and laboratory monitoring. KPIs examining functional status using the Childhood Health Assessment Questionnaire (CHAQ), quality of life, uveitis, and patient satisfaction were excluded due to concerns about feasibility of measurement.

Conclusions
The proposed KPIs build upon existing KPIs and address important processes of care that should be measured to improve the quality of JIA care. The feasibility of capturing these measures will be tested in various data sources including the Understanding Childhood Arthritis Network (UCAN) studies. Subsequent work should focus on development of meaningful outcome KPIs to drive JIA quality improvement in Canada and beyond.
Low frequency of flares during pregnancy and post-partum in stable lupus patients
Authors: Davis-Porada Julia , Kim Mimi Y. , Guerra Marta M. , Laskin Carl A. , Petri Michelle , Lockshin Michael D. , Sammaritano Lisa R. , Branch D. Ware , Sawitzke Allen , Merrill Joan T. , Buyon Jill P. , Salmon Jane E. 
Published: March 2020

Abstract
Background
Lupus patients are at risk for pregnancy loss, and it has been generally accepted that women with SLE should have low disease activity prior to conception. However, there are conflicting results regarding the effect of pregnancy on SLE flares. This study aims to identify predictors of flares during and after pregnancy in SLE patients with inactive or stable disease activity during the first trimester and to characterize and estimate the frequency of post-partum flares in these patients.

Methods
SLE patients in the multicenter, prospective PROMISSE (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus) study were evaluated for flares during and after pregnancy using the SELENA-SLEDAI Flare Index. Flares during pregnancy were assessed in all 384 patients and post-partum flares in 234 patients with study visits 2–6 months post-partum. Logistic regression models were fit to the data to identify independent risk factors for flare.

Results
During pregnancy, 20.8% of patients had mild/moderate flares and 6.25% had severe. Post-partum, 27.7% of patients had mild/moderate flares and 1.7% had severe. The mild flares rarely required treatment. Younger age, low C4 and higher PGA at baseline were independently associated with higher risk of having at least one mild/moderate or severe flare during pregnancy. Older patients were at decreased risk of flare, as well as those with quiescent disease at baseline. No variables evaluated at baseline or the visit most proximal to delivery was significantly associated with risk of flare post-partum. Medications were not associated with flare during or after pregnancy.

Conclusion
In patients with inactive or stable mild disease activity at the time of conception, lupus disease flares during and after pregnancy are typically mild and occur at similar rates. Flares during pregnancy are predicted by the patients’ age and clinical and serological activity at baseline.
Among territorial project and architectural design
Authors: Valentino Michele , Lutzoni Laura 
Published: March 2020

AbstractThe contribution develops a reflection on the urban space project in contexts characterized by historical-cultural relevance by exploring interdisciplinary approaches through the intersection of research and didactic actions in the field, which make the project emerge from specific ways of interacting with local societies. These relationships find a sense starting from the identification of some traditionally configured places in the city that present obsolete functions or abandoned conditions, but characterized by a strong urban value and can become hubs of potential and learning laboratories. In this sense, knowledge can be a tool capable of favouring forms of social relations and initiating the construction of new citizenships.The research identifies in the context of the historic city of Sassari some nuclei of urbanity, spaces and significant areas of the city that more than others recall an educational dimension. The relationship between the formative character of the historic city and the emergence of new forms of sociality favours the possibility of identifying areas outside standardization that contain the genetic code of urban conviviality. In this perspective, public space defined as the place of production of sociality, designed to bring out a different urban organization.The identification of these latent traces of a system full of meaning and full of potential for urban life can open fertile perspectives to think of new spaces of relationship for active participation in the project of the city. Marking the distance from an object-oriented position in favor of an ontology of urban and territorial relations, the project continuously aimed at revealing new forms of spatial distribution that relate different nuclei, interpreting their specific role in the overall system of generative structures environmental aspects of the city.
Changing structures of B2B networks in the Japanese textile and apparel industry
Authors: Ogai Yusaku , Matsumura Yoshiyuki , Hoshino Yusuke 
Published: March 2020

AbstractThe aim of the present study was to evaluate how the business-to-business (B2B) networks in the Japanese textile and apparel industry changed between 2005 and 2010 using data on 200 companies. Network analysis was used to study the properties of the B2B networks, and how their structures changed was characterized using the USD/JPY exchange rate. The network analysis revealed power-law properties of the B2B networks, and the core networks characterized by the largest degree centrality exhibited positive correlations with the USD/JPY exchange rate. By contrast, the peripheral networks characterized by the network path length exhibited the negative correlations with the exchange rate USD/JPY. Therefore, the changes that occurred in the B2B networks are explained as the complementarity of comparative advantages originating in the USD/JPY exchange rate. Moreover, the USD/JPY exchange rate affected the B2B networks through not only the complementarity of importing and exporting but also by changing the structures.
Factors associated with dietary adherence to the guidelines for prevention and treatment of hypertension among Korean adults with and without hypertension
Authors: Shim Jee-Seon , Heo Ji Eun , Kim Hyeon Chang 
Published: March 2020

Abstract
Background
Although dietary modification is strongly recommended for prevention and treatment of hypertension, little is known about which factors are associated with adherence to dietary guidelines. We investigated knowledge and attitude, perceived benefits of, barriers to, and self-efficacy of dietary therapy, and identified the factors associated with dietary adherence among adults with and without hypertension.

Methods
We collected information on the knowledge/attitudes and perceived benefits of dietary therapy, as well as barriers to and self-efficacy regarding dietary adherence from 497 middle-aged (34–69 years) adults who participated in the follow-up examination of the Cardiovascular and Metabolic Diseases Etiology Center (CMERC) cohort study during December 2018 and February 2019.

Results
Among people without hypertension, 95.5% (343/359) and 95.8% (344/359) answered that they would limit sodium intake and consume health diet, respectively, if diagnosed hypertension. However, among people with hypertension, only 79.7% (110/138) and 77.5% (107/138) reported they were limiting dietary sodium intake and having healthy diet, respectively. Frequency of diet management was not different between normotensive (34.0%) and hypertensive (35.5%) groups. Compared to normotensives, hypertensive people were more likely to have lower dietary adherence score, think they need to change their diet, think dietary change impossible, and report lower self-efficacy for following diet guidelines. Dietary management was significantly associated with cardiometabolic risk factors (OR: 1.63) and dietary education (OR: 2.19) among normotensives, while it was associated only with awareness that lifestyle modification is necessary regardless of antihypertensive medication (OR: 6.29) among hypertensive people. Good dietary adherence had significant associations with perceived barriers (OR: 0.71), self-efficacy (OR: 3.71), and dietary education (OR: 1.98) among normotensives; and with perceived barriers (OR: 0.54), self-efficacy (OR: 4.06), and dietary management (OR: 4.16) among hypertensive people.

Conclusions
Many Koreans have relatively low adherence to dietary guidelines for hypertension prevention and treatment. Knowledge, dietary practices, and factors affecting dietary adherence were different between adults with and without hypertension. A targeted approach will be needed to improve blood pressure control of the Korean population.