bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical profiles and quality of care of subjects with type 2 diabetes according to their cardiovascular risk: an observational, retrospective study
Authors: Pintaudi Basilio , Scatena Alessia , Piscitelli Gabriella , Frison Vera , Corrao Salvatore , Manicardi Valeria , Graziano Giusi , Rossi Maria Chiara , Gallo Marco , Mannino Domenico , Di Bartolo Paolo , Nicolucci Antonio 
Published: March 2021

Abstract
Background
The European Society of Cardiology (ESC) recently defined cardiovascular risk classes for subjects with diabetes. Aim of this study was to explore the distribution of subjects with type 2 diabetes (T2D) by cardiovascular risk groups according to the ESC classification and to describe the quality indicators of care, with particular regard to cardiovascular risk factors.

Methods
The study is based on data extracted from electronic medical records of patients treated at the 258 Italian diabetes centers participating in the AMD Annals initiative. Patients with T2D were stratified by cardiovascular risk. General descriptive indicators, measures of intermediate outcomes, intensity/appropriateness of pharmacological treatment for diabetes and cardiovascular risk factors, presence of other complications and overall quality of care were evaluated.

Results
Overall, 473,740 subjects with type 2 diabetes (78.5% at very high cardiovascular risk, 20.9% at high risk and 0.6% at moderate risk) were evaluated. Among people with T2D at very high risk: 26.4% had retinopathy, 39.5% had albuminuria, 18.7% had a previous major cardiovascular event, 39.0% had organ damage, 89.1% had three or more risk factors. The use of DPP4-i markedly increased as cardiovascular risk increased. The prescription of secretagogues also increased and that of GLP1-RAs tended to increase. The use of SGLT2-i was still limited, and only slightly higher in subjects with very high cardiovascular risk. The overall quality of care, as summarized by the Q score, tended to be lower as the level of cardiovascular risk increased.

Conclusions
A large proportion of subjects with T2D is at high or very high risk. Glucose-lowering drug therapies seem not to be adequately used with respect to their potential advantages in terms of cardiovascular risk reduction. Several actions are necessary to improve the quality of care.
A participatory approach to address within‐country cross‐border malaria: the case of Menoreh Hills in Java, Indonesia
Authors: Ahmad Riris Andono , Ferdiana Astri , Surendra Henry , Sy Tyrone Reden , Herbianto Deni , Rahayujati Theodola Baning , Rejeki Dwi Sarwani Sri , Murhandarwati E. Elsa Herdiana 
Published: March 2021

Abstract
Background
Malaria remains a significant public health issue in Indonesia. Most of the endemic areas are in the eastern parts of Indonesia, but there are a few remaining foci of persistent endemic malaria in Java, particularly in Menoreh Hills, a region bordering three districts of two provinces on this island. Despite a commitment to build a partnership to eliminate cross-border malaria, there is a lack of understanding of how this partnership might be translated into an implementable strategic plan. The study aims to provide evidence of how a participatory approach was used to strengthen the cross-border collaboration and stakeholders’ capacity to develop a joint strategic, operational, and costing plan for cross-border malaria elimination.

Methods
A participatory action research was conducted from January to August 2017, involving participants from the village, district, provincial, and national levels. This study was conducted in seven phases, including document review, focus group discussions (FGDs), planning and costing workshops, and a dissemination meeting. A total of 44 participants from primary health centres (PHC) and 27 representatives of affected villages in three districts, 16 participants from the district and provincial malaria programmes and planning bureaus, and 11 participants from the national level were involved in the processes. Data on priority issues, costing, programme coverage, and administration were collected. Thematic coding and feedback were used for analysis.

Results
Problems identified by stakeholders included low community awareness and participation in malaria prevention, high mobility across three districts, lack of financial and human resources, lack of inter-district coordination, and poor implementation of migration surveillance. Cross-border strategies identified to address malaria were improving cross-border migration surveillance, strengthening the network, governance, and advocacy of malaria control implementation across borders, and developing the malaria information system. A working group composed of the three districts’ representatives authorized to decide on cross-border issues will be created.

Conclusions
The participatory approach was applicable in cross-border malaria planning for within-country settings and useful in enhancing stakeholders’ capacities as implementers. While done in a participatory way, the joint plan crafted was a non-binding agreement; stakeholders should advocate to ensure adequate funds are poured into mobilizing the programme.
Improved gene delivery to K-562 leukemia cells by lipoic acid modified block copolymer micelles
Authors: Richter Friederike , Mapfumo Prosper , Martin Liam , Solomun Jana I. , Hausig Franziska , Frietsch Jochen J. , Ernst Thomas , Hoeppener Stephanie , Brendel Johannes C. , Traeger Anja 
Published: March 2021

AbstractAlthough there has been substantial progress in the research field of gene delivery, there are some challenges remaining, e.g. there are still cell types such as primary cells and suspension cells (immune cells) known to be difficult to transfect. Cationic polymers have gained increasing attention due to their ability to bind, condense and mask genetic material, being amenable to scale up and highly variable in their composition. In addition, they can be combined with further monomers exhibiting desired biological and chemical properties, such as antioxidative, pH- and redox-responsive or biocompatible features. By introduction of hydrophobic monomers, in particular as block copolymers, cationic micelles can be formed possessing an improved chance of transfection in otherwise challenging cells. In this study, the antioxidant biomolecule lipoic acid, which can also be used as crosslinker, was incorporated into the hydrophobic block of a diblock copolymer, poly{[2-(dimethylamino)ethyl methacrylate]101-b-[n-(butyl methacrylate)124-co-(lipoic acid methacrylate)22]} (P(DMAEMA101-b-[nBMA124-co-LAMA22])), synthesized by RAFT polymerization and assembled into micelles (LAMA-mic). These micelles were investigated regarding their pDNA binding, cytotoxicity mechanisms and transfection efficiency in K-562 and HEK293T cells, the former representing a difficult to transfect, suspension leukemia cell line. The LAMA-mic exhibited low cytotoxicity at applied concentrations but demonstrated superior transfection efficiency in HEK293T and especially K-562 cells. In-depth studies on the transfection mechanism revealed that transfection efficiency in K-562 cells does not depend on the specific oncogenic fusion gene BCR-ABL alone. It is independent of the cellular uptake of polymer-pDNA complexes but correlates with the endosomal escape of the LAMA-mic. A comparison of the transfection efficiency of the LAMA-mic with structurally comparable micelles without lipoic acid showed that lipoic acid is not solely responsible for the superior transfection efficiency of the LAMA-mic. More likely, a synergistic effect of the antioxidative lipoic acid and the micellar architecture was identified. Therefore, the incorporation of lipoic acid into the core of hydrophobic-cationic micelles represents a promising tailor-made transfer strategy, which can potentially be beneficial for other difficult to transfect cell types.
How to bring research evidence into policy? Synthesizing strategies of five research projects in low-and middle-income countries
Authors: Erismann Séverine , Pesantes Maria Amalia , Beran David , Leuenberger Andrea , Farnham Andrea , Berger Gonzalez de White Monica , Labhardt Niklaus Daniel , Tediosi Fabrizio , Akweongo Patricia , Kuwawenaruwa August , Zinsstag Jakob , Brugger Fritz , Somerville Claire , Wyss Kaspar , Prytherch Helen 
Published: March 2021

Abstract
Background
Addressing the uptake of research findings into policy-making is increasingly important for researchers who ultimately seek to contribute to improved health outcomes. The aims of the Swiss Programme for Research on Global Issues for Development (r4d Programme) initiated by the Swiss National Science Foundation and the Swiss Agency for Development and Cooperation are to create and disseminate knowledge that supports policy changes in the context of the 2030 Agenda for Sustainable Development. This paper reports on five r4d research projects and shows how researchers engage with various stakeholders, including policy-makers, in order to assure uptake of the research results.

Methods
Eleven in-depth interviews were conducted with principal investigators and their research partners from five r4d projects, using a semi-structured interview guide. The interviews explored the process of how stakeholders and policy-makers were engaged in the research project.

Results
Three key strategies were identified as fostering research uptake into policies and practices: (S1) stakeholders directly engaged with and sought evidence from researchers; (S2) stakeholders were involved in the design and throughout the implementation of the research project; and (S3) stakeholders engaged in participatory and transdisciplinary research approaches to coproduce knowledge and inform policy. In the first strategy, research evidence was directly taken up by international stakeholders as they were actively seeking new evidence on a very specific topic to up-date international guidelines. In the second strategy, examples from two r4d projects show that collaboration with stakeholders from early on in the projects increased the likelihood of translating research into policy, but that the latter was more effective in a supportive and stable policy environment. The third strategy adopted by two other r4d projects demonstrates the benefits of promoting colearning as a way to address potential power dynamics and working effectively across the local policy landscape through robust research partnerships.

Conclusions
This paper provides insights into the different strategies that facilitate collaboration and communication between stakeholders, including policy-makers, and researchers. However, it remains necessary to increase our understanding of the interests and motivations of the different actors involved in the process of influencing policy, identify clear policy-influencing objectives and provide more institutional support to engage in this complex and time-intensive process.
The consequences of compromising the EU’s free movement of persons principle on Swiss research: how to survive constrained access to regional funding
Authors: Saric Jasmina , Bolz Miriam , Waser Marco , Käser Michael 
Published: March 2021

AbstractBetween 2014 and 2016, Switzerland’s access to some of the EU funding was limited after a referendum against mass immigration was accepted and the country refused to sign the free movement accord to the EU’s newest member, Croatia. It is well documented that Switzerland has suffered from a drop in participation, funding and a decrease in consortium lead positions. However, there is no account of the consequences on institutional level. We therefore aimed at describing the immediate- and longer-term impact of the partial association status to the Swiss Tropical and Public Health Institute (Swiss TPH) and to identify key strategies for minimizing institutional damage during a limited access period to a key regional funding source. A quantitative analysis of the institute’s grants database, from 2007 to 2019, did not show any clear trends related to the partial association status of Switzerland for funding and projects awarded. The qualitative outcomes changed along the timeline assessed; whereas in 2014 a range of negative effects were stated by Swiss TPH researchers, a survey conducted in 2019 with Swiss TPH applicants and project partners to Horizon 2020, revealed that most project leaders felt that the partial association did neither affect their external partners’ willingness to collaborate nor Swiss TPH’s role in the proposal or consortium. On the other hand, the institutional strategic goal of taking on consortia leads was delayed by several years as a direct consequence of the partial association. Also, the exclusion from European research networks and the lack of consultation of expertise by the European partner institutions was widely seen as damaging. A policy of favouring long-term partnerships over ad-hoc collaborations, along with constant and trustful communication, as immediate mitigation measure, helped averting some of the reputational and access damage. Moreover, the Swiss TPH business model based on a three-way strategy of research, education and services has proven highly viable allowing to build a large pool of potential funding sources internationally, resulting in relative resilience in terms of income lost.
A novel approach to increasing community capacity for weight management a volunteer-delivered programme (ActWELL) initiated within breast screening clinics: a randomised controlled trial
Authors: Anderson Annie S. , Chong Huey Yi , Craigie Angela M. , Donnan Peter T. , Gallant Stephanie , Hickman Amy , McAdam Chloe , McKell Jennifer , McNamee Paul , Macaskill E. Jane , Mutrie Nanette , O’Carroll Ronan E. , Rauchhaus Petra , Sattar Naveed , Stead Martine , Treweek Shaun 
Published: March 2021

Abstract
Background
It is estimated that around 30% of breast cancers in post-menopausal women are related to lifestyle. The breast cancer-pooling project demonstrated that sustained weight loss of 2 to 4.5 kg is associated with an 18% lower risk of breast cancer, highlighting the importance of small changes in body weight. Our study aimed to assess the effectiveness a volunteer-delivered, community based, weight management programme (ActWELL) for women with a BMI > 25 kg/m2 attending NHS Scotland Breast Screening clinics.

Methods
A multicentre, 1:1 parallel group, randomised controlled trial was undertaken in 560 women aged 50 to 70 years with BMI > 25 kg/m2. On completion of baseline measures, all participants received a breast cancer prevention leaflet. Intervention group participants received the ActWELL intervention which focussed on personalised diet advice and pedometer walking plans. The programme was delivered in leisure centres by (the charity) Breast Cancer Now volunteer coaches.
Primary outcomes were changes between groups at 12 months in body weight (kg) and physical activity (accelerometer measured step count).

Results
Two hundred seventy-nine women were allocated to the intervention group and 281 to the comparison group. Twelve-month data were available from 240 (81%) intervention and 227 (85%) comparison group participants. Coaches delivered 523 coaching sessions and 1915 support calls to 279 intervention participants. Mean weight change was − 2.5 kg (95% CI − 3.1 to − 1.9) in the intervention group and − 1.2 kg (− 1.8 to 0.6) in the comparison group. The adjusted mean difference was − 1.3 kg (95% CI − 2.2 to − 0.4, P = 0.003). The odds ratio for losing 5% weight was 2.20 (95% CI 1.4 to 3.4, p = 0.0005) in favour of the intervention. The adjusted mean difference in step counts between groups was 483 steps/day (95% CI − 635 to 1602) (NS).

Conclusions
A community weight management intervention initiated at breast screening clinics and delivered by volunteer coaches doubled the likelihood of clinically significant weight loss at 12 months (compared with usual care) offering significant potential to decrease breast cancer risk.

Trial registration
Database of registration: ISCRTN.
Registration number:11057518.
Date trial registered:21.07.2017.
Date of enrolment of first participant: 01.09.2017.
M2 macrophage-derived exosomal microRNAs inhibit cell migration and invasion in gliomas through PI3K/AKT/mTOR signaling pathway
Authors: Yao Jie , Wang Zefen , Cheng Yong , Ma Chao , Zhong Yahua , Xiao Yilei , Gao Xu , Li Zhiqiang 
Published: March 2021

Abstract
Background
Glioma, the most common primary brain tumor, account Preparing figures for 30 to 40% of all intracranial tumors. Herein, we aimed to study the effects of M2 macrophage-derived exosomal microRNAs (miRNAs) on glioma cells.

Methods
First, we identified seven differentially expressed miRNAs in infiltrating macrophages and detected the expression of these seven miRNAs in M2 macrophages. We then selected hsa-miR-15a-5p (miR-15a) and hsa-miR-92a-3p (miR-92a) for follow-up studies, and confirmed that miR-15a and miR-92a were under-expressed in M2 macrophage exosomes. Subsequently, we demonstrated that M2 macrophage-derived exosomes promoted migration and invasion of glioma cells, while exosomal miR-15a and miR-92a had the opposite effects on glioma cells. Next, we performed the target gene prediction in four databases and conducted target gene validation by qRT-PCR, western blot and dual luciferase reporter gene assays.

Results
The results revealed that miR-15a and miR-92a were bound to CCND1 and RAP1B, respectively. Western blot assays demonstrated that interference with the expression of CCND1 or RAP1B reduced the phosphorylation level of AKT and mTOR, indicating that both CCND1 and RAP1B can activate the PI3K/AKT/mTOR signaling pathway.

Conclusion
Collectively, these findings indicate that M2 macrophage-derived exosomal miR-15a and miR-92a inhibit cell migration and invasion of glioma cells through PI3K/AKT/mTOR signaling pathway.
Appropriate margin for planning target volume for breast radiotherapy during deep inspiration breath-hold by variance component analysis
Authors: Ono Yuka , Yoshimura Michio , Ono Tomohiro , Fujimoto Takahiro , Miyabe Yuki , Matsuo Yukinori , Mizowaki Takashi 
Published: March 2021

Abstract
Background
This study aimed to quantify errors by using a cine electronic portal imaging device (cine EPID) during deep inspiration breath-hold (DIBH) for left-sided breast cancer and to estimate the planning target volume (PTV) by variance component analysis.

Methods
This study included 25 consecutive left-sided breast cancer patients treated with whole-breast irradiation (WBI) using DIBH. Breath-holding was performed while monitoring abdominal anterior–posterior (AP) motion using the Real-time Position Management (RPM) system. Cine EPID was used to evaluate the chest wall displacements in patients. Cine EPID images of the patients (309,609 frames) were analyzed to detect the edges of the chest wall using a Canny filter. The errors that occurred during DIBH included differences between the chest wall position detected by digitally reconstructed radiographs and that of all cine EPID images. The inter-patient, inter-fraction, and intra-fractional standard deviations (SDs) in the DIBH were calculated, and the PTV margin was estimated by variance component analysis.

Results
The median patient age was 55 (35–79) years, and the mean irradiation time was 20.4 ± 1.7 s. The abdominal AP motion was 1.36 ± 0.94 (0.14–5.28) mm. The overall mean of the errors was 0.30 mm (95% confidence interval: − 0.05–0.65). The inter-patient, inter-fraction, and intra-fractional SDs in the DIBH were 0.82 mm, 1.19 mm, and 1.63 mm, respectively, and the PTV margin was calculated as 3.59 mm.

Conclusions
Errors during DIBH for breast radiotherapy were monitored using EPID images and appropriate PTV margins were estimated by variance component analysis.
Circulating tumor DNA as a dynamic biomarker of response to palbociclib and fulvestrant in metastatic breast cancer patients
Authors: Darrigues Lauren , Pierga Jean-Yves , Bernard-Tessier Alice , Bièche Ivan , Silveira Amanda Bartolini , Michel Marc , Loirat Delphine , Cottu Paul , Cabel Luc , Dubot Coraline , Geiss Romain , Ricci Francesco , Vincent-Salomon Anne , Proudhon Charlotte , Bidard François-Clément 
Published: March 2021

Abstract
Background
Following the PALOMA-3 study results, the combination of palbociclib, a CDK4/6 inhibitor, with fulvestrant, a selective estrogen receptor degrader, has become a standard therapy in women with estrogen receptor-positive (ER+) HER2-negative (HER2−) metastatic breast cancer (MBC). Palbociclib has been shown to increase the progression-free survival (PFS) overall but no predictive biomarker of palbociclib efficacy has been validated so far. We thus evaluated whether early changes of circulating tumor DNA (ctDNA) levels are associated with palbociclib plus fulvestrant efficiency.

Methods
ER+ HER2− MBC patients were included in a prospective observational cohort before treatment initiation. Tumor response was assessed by radiological evaluation (RECIST v1.1) every 3 months. Plasma samples were collected before treatment (baseline), at day 15 (D15), at day 30 (D30), and at disease progression. We searched for somatic mutations from archived tumor tissues by targeted deep sequencing. For patients with somatic mutations identified, circulating tumor DNA (ctDNA) was tracked using digital droplet PCR. Ratios of ctDNA levels ([D15/baseline] and [D30/baseline]) were then correlated with prospectively registered patient characteristics and outcomes.

Results
Twenty-five of the 61 patients enrolled had a somatic mutation testable in plasma (NPIK3CA = 21, NTP53 = 2, NAKT1 = 2). At baseline, 84% of patients had detectable ctDNA levels but ctDNA levels had no prognostic impact on PFS (p = 0.10). Among those patients, ctDNA was still detected in 82% at D15 and 68% at D30. ctDNA clearance observed at day 30 was associated with longer PFS (HR = 7.2, 95% CI = 1.5–32.6, p = 0.004). On the contrary, a [D30/baseline] ctDNA ratio > 1 was associated with a shorter PFS (HR = 5.1, 95% CI = 1.4–18.3, p = 0.02) and all 5 patients with increased ctDNA levels at D30 showed disease progression after 3 months under palbociclib-fulvestrant. Finally, at the time of radiological tumor progression, ctDNA was detected in all patients tested.

Conclusion
Our study demonstrates that the efficiency of palbociclib and fulvestrant can be monitored by serial analyses of ctDNA before radiological evaluation and that early ctDNA variation is a prognostic factor of PFS.