bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of an app for promoting advance care planning and motivating patients to write their advance directives
Authors: Schöpfer Céline , Bollondi Catherine , Moussa Mohamed Amir , Sommer Johanna , Clavien Christine 
Published: June 2023

Abstract
Background
Accordons-nous, a smartphone app, was developed to support patients in the advance care planning (ACP) process. The app raises awareness and facilitates communication on this sensitive topic. It helps patients express their values and preferences for care and write their advance directives (AD).

Objective
Measure the impact of distributing Accordons-nous on patients’ propensity to engage in the ACP process, compared with the distribution of a leaflet. A secondary objective was to test the effect of socio-demographic factors (age, health status, gender, level of education) on propensity to engage in ACP.

Methods
Pre-post randomized control study. Participants were patients approached in medical waiting rooms. They received the app (treatment) or an information leaflet (control). They responded to two questionnaires: one at recruitment and a second 3–4 weeks later. Improvement on four variables relevant to ACP was measured: reported contemplation of an event relevant to ACP; decision about treatment in case of that event; discussion about it with relatives or health care professionals; writing advance directives. Statistical analysis included between-group comparisons of pre-post differences with 2-sample tests for equality of proportions and logistic regression models.

Results
Four hundred seventy three participants were recruited and full responses obtained from 312. Overall, the intervention (control and treatment together) had a positive effect on the mean reported ACP engagement for all variables: new or renewed contemplation 54%; increase in decision 8%, discussion 11%, and writing 1%, compared to the baseline. Compared to the control (leaflet), the treatment group (app) had a larger effect size for all variables: between-group difference in contemplation + 11% (logistic regression, p = .05), decision + 1% (but p > .05 on this variable), discussion + 5% (p = .05), and writing AD + 5% (p = .03). Moreover, greater age was positively correlated with having written AD at inclusion (21% among retired compared to 2% among young adults) and with the propensity to write AD after our intervention (logistic regression, p = .001). Other factors tested (frequency of consultations, gender, level of education) had no effect on participants’ ACP engagement.

Conclusions
When distributed without specific counselling, the tool increased reported ACP engagement, although effect sizes remain modest. Further studies are needed to investigate whether the app could generate greater ACP engagement if used by professionals in dedicated ACP consultations.
The role of m6A methylation in therapy resistance in cancer
Authors: Zhuang Hengzhao , Yu Bo , Tao Dan , Xu Xiaoyan , Xu Yijun , Wang Jian , Jiao Yang , Wang Lili 
Published: June 2023

AbstractCancer therapy resistance is the main cause of cancer treatment failure. The mechanism of therapy resistance is a hot topic in epigenetics. As one of the most common RNA modifications, N6-methyladenosine (m6A) is involved in various processes of RNA metabolism, such as stability, splicing, transcription, translation, and degradation. A large number of studies have shown that m6A RNA methylation regulates the proliferation and invasion of cancer cells, but the role of m6A in cancer therapy resistance is unclear. In this review, we summarized the research progress related to the role of m6A in regulating therapy resistance in cancers.
Evidence synthesis to policy: development and implementation of an impact-oriented approach from the Eastern Mediterranean Region
Authors: El-Jardali Fadi , Fadlallah Racha , Bou Karroum Lama , Akl Elie A. 
Published: June 2023

Abstract
Background
Despite the importance of evidence syntheses in informing policymaking, their production and use remain limited in the Eastern Mediterranean region (EMR). There is a lack of empirical research on approaches to promote and use policy-relevant evidence syntheses to inform policymaking processes in the EMR.

Objective
This study sought to describe the development of an impact-oriented approach to link evidence synthesis to policy, and its implementation through selected case studies in Lebanon, a middle-income country in the EMR.

Methods
This study followed a multifaceted and iterative process that included (i) a review of the literature, (ii) input from international experts in evidence synthesis and evidence-informed health policymaking, and (iii) application in a real-world setting (implementation). We describe four selected case studies of implementation. Surveys were used to assess policy briefs, deliberative dialogues, and post-dialogue activities. Additionally, Kingdon’s stream theory was adopted to further explain how and why the selected policy issues rose to the decision agenda.

Results
The approach incorporates three interrelated phases: (1) priority setting, (2) evidence synthesis, and (3) uptake. Policy-relevant priorities are generated through formal priority setting exercises, direct requests by policymakers and stakeholders, or a focusing event. Identified priorities are translated into focused questions that can be addressed via evidence synthesis (phase 1). Next, a scoping of the literature is conducted to identify existing evidence syntheses addressing the question of interest. Unless the team identifies relevant, up-to-date and high-quality evidence syntheses, it proceeds to conducting SRs addressing the priority questions of interest (phase 2). Next, the team prepares knowledge translation products (e.g., policy briefs) for undertaking knowledge uptake activities, followed by monitoring and evaluation (phase 3). There are two prerequisites to the application of the approach: enhancing contextual awareness and capacity strengthening. The four case studies illustrate how evidence produced from the suites of activities was used to inform health policies and practices.

Conclusions
To our knowledge, this is the first study to describe both the development and implementation of an approach to link evidence synthesis to policy in the EMR. We believe the approach will be useful for researchers, knowledge translation platforms, governments, and funders seeking to promote evidence-informed policymaking and practice.
The choroid plexus acts as an immune cell reservoir and brain entry site in experimental autoimmune encephalomyelitis
Authors: Lazarevic Ivana , Soldati Sasha , Mapunda Josephine A. , Rudolph Henriette , Rosito Maria , de Oliveira Alex Cardoso , Enzmann Gaby , Nishihara Hideaki , Ishikawa Hiroshi , Tenenbaum Tobias , Schroten Horst , Engelhardt Britta 
Published: June 2023

AbstractThe choroid plexus (ChP) has been suggested as an alternative central nervous system (CNS) entry site for CCR6+ Th17 cells during the initiation of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS). To advance our understanding of the importance of the ChP in orchestrating CNS immune cell entry during neuroinflammation, we here directly compared the accumulation of CD45+ immune cell subsets in the ChP, the brain and spinal cord at different stages of EAE by flow cytometry. We found that the ChP harbors high numbers of CD45int resident innate but also of CD45hi adaptive immune cell subsets including CCR6+ Th17 cells. With the exception to tissue-resident myeloid cells and B cells, numbers of CD45+ immune cells and specifically of CD4+ T cells increased in the ChP prior to EAE onset and remained elevated while declining in brain and spinal cord during chronic disease. Increased numbers of ChP immune cells preceded their increase in the cerebrospinal fluid (CSF). Th17 but also other CD4+ effector T-cell subsets could migrate from the basolateral to the apical side of the blood-cerebrospinal fluid barrier (BCSFB) in vitro, however, diapedesis of effector Th cells including that of Th17 cells did not require interaction of CCR6 with BCSFB derived CCL20. Our data underscore the important role of the ChP as CNS immune cell entry site in the context of autoimmune neuroinflammation.
Development of a universal, oriented antibody immobilization method to functionalize vascular prostheses for enhanced endothelialization for potential clinical application
Authors: Zhang Qiuwang , Duncan Sebastian , Szulc Daniel A. , de Mestral Charles , Kutryk Michael JB 
Published: June 2023

Abstract
Background
Thrombosis is a common cause of vascular prosthesis failure. Antibody coating of prostheses to capture circulating endothelial progenitor cells to aid endothelialization on the device surface appears a promising solution to prevent thrombus formation. Compared with random antibody immobilization, oriented antibody coating (OAC) increases antibody-antigen binding capacity and reduces antibody immunogenicity in vivo. Currently, few OAC methods have been documented, with none possessing clinical application potential.

Results
Dopamine and the linker amino-PEG8-hydrazide-t-boc were successfully deposited on the surface of cobalt chromium (CC) discs, CC stents and expanded polytetrafluoroethylene (ePTFE) grafts under a slightly basic condition. CD34 antibodies were immobilized through the reaction between aldehydes in the Fc region created by oxidation and hydrazides in the linker after t-boc removal. CD34 antibody-coated surfaces were integral and smooth as shown by scanning electron microscopy (SEM), had significantly reduced or no substrate-specific signals as revealed by X-ray photoelectron spectroscopy, were hospitable for HUVEC growth as demonstrated by cell proliferation assay, and specifically bound CD34 + cells as shown by cell binding testing. CD34 antibody coating turned hydrophobic property of ePTFE grafts to hydrophilic. In a porcine carotid artery interposition model, a confluent monolayer of cobblestone-shaped CD31 + endothelial cells on the luminal surface of the CD34 antibody coated ePTFE graft were observed. In contrast, thrombi and fibrin fibers on the bare graft, and sporadic cells on the graft coated by chemicals without antibodies were seen.

Conclusion
A universal, OAC method was developed. Our in vitro and in vivo data suggest that the method can be potentially translated into clinical application, e.g., modifying ePTFE grafts to mitigate their thrombotic propensity and possibly provide for improved long-term patency for small-diameter grafts.
Metastatic lymph node targeted CTLA4 blockade: a potent intervention for local and distant metastases with minimal ICI-induced pneumonia
Authors: Mishra Radhika , Sukhbaatar Ariunbuyan , Mori Shiro , Kodama Tetsuya 
Published: June 2023

Abstract
Background
Immune checkpoint blockade (ICB) elicits a strong and durable therapeutic response, but its application is limited by disparate responses and its associated immune-related adverse events (irAEs). Previously, in a murine model of lymph node (LN) metastasis, we showed that intranodal administration of chemotherapeutic agents using a lymphatic drug delivery system (LDDS) elicits stronger therapeutic responses in comparison to systemic drug delivery approaches, while minimizing systemic toxicity, due to its improved pharmacokinetic profile at the intended site. Importantly, the LN is a reservoir of immunotherapeutic targets. We therefore hypothesized that metastatic LN-targeted ICB can amplify anti-tumor response and uncouple it from ICB-induced irAEs.

Methods
To test our hypothesis, models of LN and distant metastases were established with luciferase expressing LM8 cells in MXH10/Mo-lpr/lpr mice, a recombinant inbred strain of mice capable of recapitulating ICB-induced interstitial pneumonia. This model was used to interrogate ICB-associated therapeutic response and immune related adverse events (irAEs) by in vivo imaging, high-frequency ultrasound imaging and histopathology. qPCR and flowcytometry were utilized to uncover the mediators of anti-tumor immunity.

Results
Tumor-bearing LN (tbLN)-directed CTLA4 blockade generated robust anti-tumor response against local and systemic metastases, thereby improving survival. The anti-tumor effects were accompanied by an upregulation of effector CD8T cells in the tumor-microenvironment and periphery. In comparison, non-specific CTLA4 blockade was found to elicit weaker anti-tumor effect and exacerbated ICI-induced irAEs, especially interstitial pneumonia. Together these data highlight the importance of tbLN-targeted checkpoint blockade for efficacious response.

Conclusions
Intranodal delivery of immune checkpoint inhibitors to metastatic LN can potentiate therapeutic response while minimizing irAEs stemming from systemic lowering of immune activation threshold.
CREBZF mRNA nanoparticles suppress breast cancer progression through a positive feedback loop boosted by circPAPD4
Authors: Zhou Boxuan , Xue Jinhua , Wu Runxin , Meng Hongyu , Li Ruixi , Mo Zhaohong , Zhai Hang , Chen Xianyu , Liu Rongqiang , Lai Guie , Chen Xiaohong , Li Taiyuan , Zheng Shiyang 
Published: June 2023

Abstract
Background
Breast cancer (BC) negatively impacts the health of women worldwide. Circular RNAs (circRNAs) are a group of endogenous RNAs considered essential regulatory factor in BC tumorigenesis and progression. However, the underlying molecular mechanisms of circRNAs remain unclear.

Methods
Expression levels of circPAPD4, miR-1269a, CREBZF, and ADAR1 in BC cell lines and tissues were measured using bioinformatics analysis, RT-qPCR, ISH, and IHC. Cell proliferation and apoptosis were measured using CCK8, EdU staining, flow cytometry, and TUNEL assays. Pearson correlation analysis, RNA pull-down, dual-luciferase reporter, and co-immunoprecipitation assays were used to explore the correlation among circPAPD4, miR-1269a, CREBZF, STAT3, and ADAR1. Effects of circPAPD4 overexpression on tumor progression were investigated using in vivo assays. Moreover, CREBZF mRNA delivered by polymeric nanoparticles (CREBZF-mRNA-NPs) was used to examine application value of our findings.

Results
CircPAPD4 expression was low in BC tissues and cells. Functionally, circPAPD4 inhibited proliferation and promoted apoptosis in vitro and in vivo. Mechanistically, circPAPD4 biogenesis was regulated by ADAR1. And circPAPD4 promoted CREBZF expression by competitively binding to miR-1269a. More importantly, CREBZF promoted circPAPD4 expression by suppressing STAT3 dimerization and ADAR1 expression, revealing a novel positive feedback loop that curbed BC progression. Systematic delivery of CREBZF-mRNA-NPs effectively induced CREBZF expression and activated the positive feedback loop of circPAPD4/miR-1269a/CREBZF/STAT3/ADAR1, which might suppress BC progression in vitro and in vivo.

Conclusion
Our findings firstly illustrated that circPAPD4/miR-1269a/CREBZF/STAT3/ADAR1 positive feedback loop mediated BC progression, and delivering CREBZF mRNA nanoparticles suppressed BC progression in vitro and in vivo, which might provide novel insights into therapeutic strategies for breast cancer.
Real-life drug retention rate and safety of rituximab when treating rheumatic diseases: a single-centre Swiss retrospective cohort study
Authors: Dumusc Alexandre , Alromaih Fahad , Perreau Matthieu , Hügle Thomas , Zufferey Pascal , Dan Diana 
Published: June 2023

Abstract
Background
In Switzerland, rituximab (RTX) is licenced for the treatment of rheumatoid arthritis (RA) and ANCA-associated vasculitis (AAV) but is frequently used off-label to treat other auto-immune diseases (AID), especially connective tissue diseases (CTD). We aimed to characterise the use of RTX in AID in a real-life Swiss setting and compare RTX retention rates and safety outcomes between patients treated for RA, CTD and AAV.

Methods
A retrospective cohort study of patients who started RTX in the Rheumatology Department for RA or AID. The RTX retention rate was analysed using Kaplan–Meier survival curves. Occurrences of serious adverse events (SAE), low IgG levels and anti-drug antibodies (ADA) were reported.

Results
Two hundred three patients were treated with RTX: 51.7% had RA, 29.6% CTD, 9.9% vasculitis and 8.9% other AIDs. The total observation time was 665 patient-years. RTX retention probability at 2 years (95%CI) was similar for RA and CTD 0.65 (0.55 to 0.73), 0.60 (0.47 to 0.72) and lower for vasculitis 0.25 (0.09 to 0.45). Survival curves for RTX retention matched closely (p = 0.97) between RA and CTD patients but were lower for patients with vasculitis due to a higher percentage of induced remission. Patients with vasculitis (95%) and CTD (75%) had a higher rate of concomitant glucocorticoid use than RA (60%). Moderate to severe hypogammaglobulinaemia was observed more frequently in patients with vasculitis (35%) than with RA (13%) or CTD (9%) and was associated with an increased risk of presenting a first infectious SAE (HR 2.01, 95% CI 1.04 to 3.91). The incidence rate of SAE was 23.3 SAE/100 patient-years (36% were infectious). When searched, ADAs were observed in 18% of the patients and were detected in 63% of infusions-related SAE. 10 patients died during RTX treatment and up to 12 months after the last RTX infusion, 50% from infection.

Conclusion
RTX retention rates are similar for patients with RA and CTD but lower for those with vasculitis due to more frequent remission. Patients treated with RTX for vasculitis present more SAE and infectious SAE than patients with RA and CTD, potentially due to a higher use of concomitant glucocorticoids and the occurrence of hypogammaglobulinaemia.
Higher β cell death in pregnant women, measured by DNA methylation patterns of cell-free DNA, compared to new-onset type 1 and type 2 diabetes subjects: a cross-sectional study
Authors: Linares-Pineda Teresa María , Gutiérrez-Repiso Carolina , Peña-Montero Nerea , Molina-Vega María , Rubio Fuensanta Lima , Arana María Suárez , Tinahones Francisco J. , Picón-César María José , Morcillo Sonsoles 
Published: June 2023

AbstractDiabetes is a metabolic disorder of glucose homeostasis in which β cell destruction occurs silently and is detected mainly when symptoms appear. In the last few years, it has emerged a great interest in developing markers capable of detecting pancreatic β cell death focused on improving early diagnosis and getting a better treatment response, mainly in type 1 diabetes. But other types of diabetes would also benefit from early detection of β cell death. Differentially methylated circulating DNA is being studied as minimally invasive biomarker of cell death. We aimed to explore whether the unmethylated/methylated ratio of the insulin and amylin genes might be a good biomarker of β cell death in different types of diabetes. A lower index ∆Ct indicates a higher rate of β-cell death. Plasma samples from subjects without diabetes, pregnant women, pregnant with gestational diabetes (GDM), type 1 diabetes and type 2 diabetes were analyzed. A qPCR reaction with specific primers for both methylated and unmethylated fragments of insulin and amylin genes were carried out. Pregnant women, GDM and non- GDM, showed a higher β-cell death for both markers (∆INS = 3.8 ± 2.1 and ∆Amylin = 8.5 ± 3.6), whereas T1D presented lower rate (∆INS = 6.2 ± 2.1 and ∆Amylin = 10.7 ± 2.9) comparable to healthy subjects. The insulin methylation index was associated with the newborn birth weight (r = 0.46; p = 0.033) and with insulin resistance (r = -0.533; p = 0.027) in the GDM group. The higher rate of β-cell death was observed in pregnant women independently of their metabolic status. These indexes could be a good indicator of β cell death in processes caused by defects on insulin secretion, insulin action, or both.
The impact of perceived social support and coping on distress in a sample of Atlantic Canadian health professional students during COVID-19 compared to pre-COVID peers
Authors: Button Pamela , Fallon Laura , Fowler Ken 
Published: June 2023

Abstract
Purpose
Students pursuing higher education and health professional (HP) programs (e.g., nursing, pharmacy, social work, medicine) experience stressors including academic pressures, workload, developing professional competencies, professional socialization, the hidden curriculum, entering clinical practice and navigating relationships with colleagues. Such stress can have detrimental effects on HP students physical and psychological functioning and can adversely affect patient care. This study examined the role of perceived social support and resilience in predicting distress of Atlantic Canadian HP students during the COVID-19 pandemic and compared the findings to a pre-COVID population of age and sex matched Canadians.

Method
Second year HP students (N = 93) completed a survey assessing distress, perceived social support, and resilience and open-ended questions on student awareness of supports and counselling available to them, their use/barriers to the services, and the impact of COVID-19 on their personal functioning. HP student responses were also compared with age and sex matched Canadian peers from data collected prior to COVID-19.

Results
It was found that HP students reported moderate to severe psychological distress, and while they reported high levels of social support on a measure of perceived social support they also reported that the COVID-19 pandemic made them feel isolated and that they lacked social support. It was found that the sample of HP students reported significantly higher psychological distress than the mean scores of the age and sex matched sample of Canadian peers.

Conclusions
These findings call for creation of more tailored interventions and supports for HP students.