bluuebunny/crossref_metadata_2025_split huggingface dataset:
The efficacy of strength or aerobic exercise on quality of life and knee function in patients with knee osteoarthritis. A multi-arm randomized controlled trial with 1-year follow-up
Authors: Øiestad Britt Elin , Årøen Asbjørn , Røtterud Jan Harald , Østerås Nina , Jarstad Even , Grotle Margreth , Risberg May Arna 
Published: September 2023

Abstract
Objective
To evaluate the efficacy of strength exercise or aerobic exercise compared to usual care on knee-related quality of life (QoL) and knee function at 4 months and 1 year in individuals with knee osteoarthritis.

Methods
A three-arm randomized controlled trial (RCT) compared 12 weeks of strength exercise or aerobic exercise (stationary cycling) to usual care supervised by physiotherapists in primary care. We recruited 168 participants aged 35–70 years with symptomatic knee osteoarthritis. The primary outcome was The Knee Injury and Osteoarthritis Outcome Score (KOOS) QoL at 1 year. Secondary outcomes were self-reported function, pain, and self-efficacy, muscle strength and maximal oxygen uptake (VO2max) at 4 months and 1 year.

Results
There were no differences between strength exercise and usual care on KOOS QoL (6.5, 95% CI -0.9 to 14), or for aerobic exercise and usual care (5.0, 95% CI -2.7 to 12.8), at 1 year. The two exercise groups showed better quadriceps muscle strength, and VO2max at 4 months, compared to usual care.

Conclusion
This trial found no statistically significant effects of two exercise programs compared to usual care on KOOS QoL at 1 year in individuals with symptomatic and radiographic knee osteoarthritis, but an underpowered sample size may explain lack of efficacy between the intervention groups and the usual care group.

ClinicalTrials.gov Identifier
NCT01682980.
Influence of surface nanotopography and wettability on early phases of peri-implant soft tissue healing: an in-vivo study in dogs
Authors: Wang Caiyun , Wang Xin , Lu Ran , Cao Xu , Yuan Dingxiang , Chen Su 
Published: September 2023

Abstract
Background
It is well established that nanotopography and wettability of implant surfaces contribute to osseointegration and long-term implant success. However, the effects of a hydrogenated surface with nanotubular and superhydrophilic properties on peri-implant soft tissue remain unclear. This study was designed to study the impact of a modified abutment surface on early soft tissue integration compared with a machined surface.

Methods
Thirty-six implants were placed at the bone level in the bilateral mandible of six beagles, followed by healing abutments belonging to the standard machined Ti-6Al-4V alloy abutments (TC4-M), anodized abutments with nanotubes (TC4-Nano), and hydrogenated abutments (TC4-H/Nano) groups, which were randomly screwed to the implants. After two and four weeks of wound healing, the animals were euthanized for histological evaluation.

Results
A superhydrophilic nanotubular surface developed on the hydrogenated abutment. Histological and histometric analyses revealed similar peri-implant soft tissue healing and dimensions for the three types of abutments at two and four weeks. Connective tissue (CT) length was longer around TC4-H/Nano abutments compared with standard abutments; however, the differences were not statistically significant. Moreover, collagen fibers in the TC4-H/Nano group extended and were attached perpendicularly to the superhydrophilic surface.

Conclusions
Our results revealed that the soft tissue interface adjacent to the hydrogenated abutment is comparable to that of the machined abutment. A tendency of increased CT length and perpendicular collagen fibers was observed around the modified abutment. This study suggests that nanotubular/superhydrophilic surfaces could be a promising modification to enhance soft tissue sealing. However, comprehensive studies should be conducted to evaluate the peri-implant soft tissue around the modified abutment immunohistochemically, histopathologically, and clinically.
Health literacy education at the time of COVID-19: development and piloting of an educational programme for university health professional students in 4 European countries
Authors: Papa Roberta , Sixsmith Jane , Giammarchi Cinzia , Lippke Sonia , McKenna Verna , Di Furia Lucia , Ceravolo Maria Gabriella , De Winter Andrea 
Published: September 2023

Abstract
Background
Health literacy has a strong influence on individual health outcomes and the sustainability of healthcare systems. Healthcare professionals often overestimate patients’ health literacy levels and lack adequate competencies to address limited health literacy effectively. Therefore, promoting understanding through effective health communication between professionals and citizens is becoming increasingly important. Although health literacy has recently gained more attention, health literacy educational programmes targeting future healthcare professionals are still scarce, especially in Europe. This study describes the piloting process of a pan-European health literacy educational programme and shows how the educational material is being used during time of crisis such as the COVID-19 pandemic.

Methods
The educational programme was developed through the definition of an educational philosophy and iterative co-creation processes consisting of stakeholders’ consultations, material development and pilots with students. The evaluation was carried out in Italy through four pilot tests involving 107 students of health-related degrees. An evaluation questionnaire and a pre-post test were developed and used to collect students’ and educators’ feedback (quantitative and qualitative) and assess changes in health literacy awareness, respectively. Three additional pilots were organized in Italy and Germany mostly during the COVID-19 pandemic to evaluate the feasibility of the educational programme through online and hybrid learning, respectively.

Results
The pilots received positive feedback from both students and educators. Students were highly satisfied with the courses, reported their relevance for their future profession and appreciated the interactive teaching methods. The pre-post test showed a significant improvement in health literacy awareness after the training. Educators reported the adequacy and flexibility of the training material, the ease of transferability of the content of the lessons into practice, and the validity of the tested options to integrate the educational programme into the curricula.

Conclusions
Our comprehensive, evidence-based educational programme contributes to addressing the existing challenges in Europe, and its flexibility allows for easy integration in the curricula, through different options, hence supporting a widespread uptake in the European Union and maybe beyond. Health literacy education is a useful tool to improve citizens’ access to healthcare information and services, achieve better health outcomes and support healthcare systems’ sustainability.
Investigation of physical playfulness in physiotherapy students
Authors: Karaali Hayriye Kul , Ozcan Ozlem 
Published: September 2023

Abstract
Background
Physiotherapists show a positive attitude towards playing games in order to be a role model for pediatric patients and to increase the success of therapy. The aim of the present study is to investigate the physical playfulness of physiotherapy students and the relationship of physical playfulness and individual and environmental factors.

Methods
The sociodemographic data, regular physical activity habits of the students were examined as well as their computer game playing status and duration. “Attitudes of 18–22 Age Adults for Playing Games That Contain Physical Activity” scale was used for assessing playfulness.

Results
A total of 268 students participated in the study. Among the game proneness scale subsections, the highest score was obtained in the Social Adjustment while the lowest scores were obtained in the “Desire to Play Game” and “To take pleasure from playing game” subsections. Male students scored higher in “Risk Taking and “To take pleasure from playing game” in comparison with the female students. There was a statistically significant difference between physical activity habits and “Game Compassion”, “Risk Taking”, “Social Adjustment” and “To take pleasure from playing game scores”.

Conclusion
Physiotherapy students were found to be more playful, particularly in terms of social adaptation. Men take more risks in the plays and also play the games more enjoyable. Students with regular physical activity habits were more playful overall. The present study suggests that monitoring physical activity levels, computer games types might be beneficial for evaluating the playfulness.
Are the stars aligned? Healthcare students’ conditions for negotiating tasks and competencies during interprofessional clinical placement
Authors: Törnqvist Tove , Lindh Falk Annika , Jensen Catrine Buck , Iversen Anita , Tingström Pia 
Published: September 2023

Abstract
Background
Healthcare students must learn to collaborate across professional boundaries so they can make use of each other’s knowledge and competencies in a way that benefits the patient. One aspect of interprofessional collaboration implies negotiating what needs to be done and by whom. Research, focused on the conditions under which students perform this negotiation when they are working together during interprofessional clinical placement, needs to be further developed. The study therefore aimed to explore students’ negotiation of tasks and competencies when students are working together as an interprofessional team during clinical placement.

Methods
The study was designed as a focused ethnographic observational study. Two Nordic sites where final-year healthcare students perform clinical interprofessional education were included. Data consists of fieldnotes, together with informal conversations, group, and focus group interviews. In total, 160 h of participating observations and 3 h of interviews are included in the study. The analysis was informed by the theory on communities of practice.

Results
Students relate to intersecting communities of practice when they negotiate what they should do to help a patient and who should do it. When the different communities of practice align, they support students in coming to an agreement. However, these communities of practice sometimes pulled the students in different directions, and negotiations were sometimes interrupted or stranded. On those occasions, observations show how the interprofessional learning practice conflicted with either clinical practice or one of the student’s profession-specific practices. Conditions that had an impact on whether or not communities of practice aligned when students negotiated these situations proved to be ‘having time to negotiate or not’, as well as ‘feeling safe or not’.

Conclusions
Final-year healthcare students can negotiate who in the team has the competence suited for a specific task. However, they must adapt their negotiations to different communities of practice being enacted at the same time. Educators need to be attentive to this and make an effort to ensure that students benefit from these intersecting communities of practice, both when they align and when they are in conflict.
Investigating the acceptance and use of massive open online courses (MOOCs) for health informatics education
Authors: Alharbi Ali H 
Published: September 2023

Abstract
Background
This study investigated the acceptance and use of massive open online courses (MOOCs) among health informatics educators and students in Saudi Arabian academic institutions. A theoretical model based on the unified theory of acceptance and use of technology (UTAUT), self-determination theory (SDT), and channel expansion theory (CET) was used to identify factors that affect MOOC adoption in health informatics education.

Methods
A survey research design was employed, and cross-sectional data were collected from health informatics instructors and students in academic institutions in Saudi Arabia. A total of 145 completed responses were used in the final analysis of the data.

Results
The findings indicated that performance and effort expectancy were important factors that could predict the acceptance and use of MOOCs among health informatics instructors and students. Additionally, perceived media richness affected the actual use of health informatics MOOCs among students and instructors in Saudi Arabian academic institutions. The results of this study show that autonomy, relatedness, and competence must be considered in the design of health informatics MOOCs.

Conclusions
A combination of these models can effectively explain the adoption and use of MOOCs in emerging fields such as health informatics.
Exploiting immunostimulatory mechanisms of immunogenic cell death to develop membrane-encapsulated nanoparticles as a potent tumor vaccine
Authors: Liu Qingwen , Hu Yongmao , Zheng Peng , Yang Ying , Fu Yuting , Yang Ying , Duan Biao , Wang Mengzhen , Li Duo , Li Weiran , He Jinrong , Zheng Xiao , Long Qiong , Ma Yanbing 
Published: September 2023

AbstractVaccine is one of the most promising strategies for cancer immunotherapy; however, there are no therapeutic cancer vaccine achieving significant clinical efficacy till now. The main limiting factors include the immune suppression and escape mechanisms developed by tumor and not enough capacity of vaccines to induce a vigorous anti-tumor immunity. This study aimed to develop a strategy of membrane-based biomimetic nanovaccine and investigate the immunological outcomes of utilizing the unique immunostimulatory mechanisms derived of immunogenic cell death (ICD) and of fulfilling a simultaneous nanoscale delivery of a highlighted tumor antigen and broad membrane-associated tumor antigens in the vaccine design. TC-1 tumor cells were treated in vitro with a mixture of mitoxantrone and curcumin for ICD induction, and then chitosan (CS)-coated polylactic co-glycolic acid (PLGA) nanoparticles loaded with HPV16 E744-62 peptides were decorated with the prepared ICD tumor cell membrane (IM); further, the IM-decorated nanoparticles along with adenosine triphosphate (ATP) were embedded with sodium alginate (ALG) hydrogel, And then, the immunological features and therapeutic potency were evaluated in vitro and in vivo. The nanovaccine significantly stimulated the migration, antigen uptake, and maturation of DCs in vitro, improved antigen lysosome escape, and promoted the retention at injection site and accumulation in LNs of the tumor antigen in vivo. In a subcutaneously grafted TC-1 tumor model, the therapeutic immunization of nanovaccine elicited a dramatical antitumor immunity. This study provides a strategy for the development of tumor vaccines.
Graphical Abstract
Enhanced therapeutic effect of PEDF-loaded mesenchymal stem cell-derived small extracellular vesicles against oxygen-induced retinopathy through increased stability and penetrability of PEDF
Authors: Fan Ruiyan , Su Lin , Zhang Hui , Jiang Yilin , Yu Zihao , Zhang Xiaomin , Li Xiaorong 
Published: September 2023

Abstract
Background
Several common retinal diseases that cause blindness are characterised by pathological neovascularisation accompanied by inflammation and neurodegeneration, including retinopathy of prematurity (ROP), diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinal vein occlusion (RVO). The current treatment strategies for these diseases have limited benefits. Thus, safer and more effective alternative approaches are required. In this study, we loaded small extracellular vesicles (sEVs) derived from mesenchymal stem cell (MSC) with pigment epithelium-derived factor (PEDF), and tested the therapeutic effect of PEDF-loaded sEVs (PEDF-sEVs) using an oxygen induced retinopathy (OIR) mouse model, aiming to establish a new therapy strategy for the treatment of retinal pathological angiogenesis.

Results
We formulated PEDF-loaded sEVs (PEDF-sEVs) containing high concentrations of PEDF and evaluated their effects through in vivo and in vitro experiments. In OIR mice, PEDF-sEVs showed significantly better effects on retinal avascular areas, inflammation, and neuronal degeneration compared with the anti-vascular endothelial growth factor (VEGF) drug, which may indicate a possible advantage of PEDF-sEVs over anti-VEGF drugs in the treatment of pathological neovascularisation. In vitro, PEDF-sEVs greatly inhibited endothelial cell (EC) proliferation, migration, and tube formation by suppressing the VEGF-induced phosphorylation of extracellular signal-regulated kinase (ERK) and AKT (also known as Protein Kinase B). All experiments and analyses were performed in triplicate. PEDF-sEVs were more effective than PEDF or sEVs alone, both in vitro and in vivo. Furthermore, to determine the distribution of PEDF-sEVs, we used DiD-labelled sEVs and FITC-labelled PEDF to track the sEVs and PEDF, respectively. We found that PEDF-sEVs effectively reduced the degradation of PEDF.

Conclusions
Loading PEDF on sEVs effectively enhanced the anti-angiogenic, anti-inflammatory, and neuroprotective effects of PEDF by increasing the stability and penetrability. These results suggest a potential role for PEDF-sEVs in retinal pathological neovascularisation.

Graphical Abstract
LMP2-mRNA lipid nanoparticle sensitizes EBV-related tumors to anti-PD-1 therapy by reversing T cell exhaustion
Authors: Xiang Yu , Tian Miaomiao , Huang Juan , Li Yueyi , Li Guangqi , Li Xue , Jiang Zedong , Song Xiangrong , Ma Xuelei 
Published: September 2023

Abstract
Background
Targeting EBV-proteins with mRNA vaccines is a promising way to treat EBV-related tumors like nasopharyngeal carcinoma (NPC). We assume that it may sensitize tumors to immune checkpoint inhibitors.

Results
We developed an LMP2-mRNA lipid nanoparticle (C2@mLMP2) that can be delivered to tumor-draining lymph nodes. C2@mLMP2 exhibited high transfection efficiency and lysosomal escape ability and induced an increased proportion of CD8 + central memory T cells and CD8 + effective memory T cells in the spleen of the mice model. A strong synergistic anti-tumor effect of C2@mLMP2 in combination with αPD-1 was observed in tumor-bearing mice. The mechanism was identified to be associated with a reverse of CD8 + T cell exhaustion in the tumor microenvironment. The pathological analysis further proved the safety of the vaccine and the combined therapy.

Conclusions
This is the first study proving the synergistic effect of the EBV-mRNA vaccine and PD-1 inhibitors for EBV-related tumors. This study provides theoretical evidence for further clinical trials that may expand the application scenario and efficacy of immunotherapy in NPC.

Graphical Abstract
Characterizing Canadian funded partnered health research projects between 2011 and 2019: a retrospective analysis
Authors: Sibley Kathryn M. , Khan Masood , Touchette Alexie J. , Crockett Leah K. , Driedger S. Michelle , Gainforth Heather L. , Prabhu Devashree , Steliga Dawn , Tefft Olivia , Graham Ian D. 
Published: September 2023

Abstract
Background and Aims
Involving research users in collaborative research approaches may increase the relevance and utility of research findings. Our primary objectives were to (i) identify and describe characteristics of Canadian federally and provincially funded health research projects that included research users and were funded between 2011 and 2019; (ii) explore changes over time; and (iii) compare characteristics between funder required and optional partnerships.

Methods
Retrospective analysis. Inclusion criteria were projects that included research users. We analyzed publicly available project variables, and coded field and type of research using established classification systems. We summarized data with descriptive statistics and compared variables across three funding year blocks and partnership requirement status.

Results
We identified 1153 partnered health research projects, representing 137 fields of research and 37 types of research categories. Most projects included a required partnership (80%) and fell into health and social care services research (66%). Project length and funding amount increased from average of 24.8 months and $266 248 CAD in 2011–2013 to 31.6 months and $438 766 CAD in 2017–2019. There were significantly fewer required partnerships in 2017–2019.

Conclusions
Between 2011 and 2019 Canadian federally and provincially funded partnered health research reflected primarily care services research across many fields. The observed breadth suggests that partnered health research approaches are applicable in many fields of research. Additional work to support partnered research across all types of health research (especially biomedical research) is warranted. The administration of larger grants that are funded for longer time periods may address previously identified concerns among research teams engaging in partnered research but may mean that fewer teams receive funding and risk delaying responding to time-sensitive data needs for users. Our process and findings can be used as a starting point for international comparison.
The effect of patient-led goal setting approach combined with pain neuroscience education or manual therapy in patients with chronic low back pain: protocol for a parallel-group randomized controlled trial
Authors: Soheili Sahar , Letafatkar Amir , Hosseinzadeh Mahdi 
Published: September 2023

Abstract
Background
Low back pain (LBP) is a multifactorial disorder associated with a high range of physical and psychological burden on the society. Patient-led goal-setting approach has shown potential effects for improving chronic LBP. However, there are few studies investigating its benefits when combined with a supplementary intervention. This paper, therefore, presents a protocol for a randomized control trial (RCT) to study the effect of a patient-led goal-setting approach combined with pain neuroscience education (PNE) or manual therapy (MT) among patients with chronic LBP.

Methods
A total of 105 patients suffering from chronic LBP will be recruited via flyers displayed in hospitals and universities, and those meeting the study’s criteria will randomly be allocated into a patient-led goal-setting approach with the PNE group, and/or with the MT program group, and/or a control group. The primary outcomes will be the pain intensity and disability. Secondary outcomes include quality of life, depression, anxiety and stress, fear avoidance beliefs, kinesophobia, pain self-efficacy, catastrophic pain, neurophysiology of pain, and central sensitivity. All the outcomes will be recorded at 2 months after receiving the treatment as post-test sessions and after 4 and 12 months as follow-up sessions. The Ethics Committee in Research at Sport Sciences Research Institute of Iran approved the protocol of this trial (IR.SSRC.REC.1400.084). Written, informed consent to participate will be obtained from all participants. All methods will be conducted in accordance with the ethical standards of the Declaration of Helsinki and in accordance with relevant guidelines and regulations. We will disseminate the findings through peer-reviewed publications and conference presentations and send them to the participants.

Discussion
This trial will demonstrate which supplementary intervention can better improve the impact of a patient-led goal-setting approach to treat LBP. If successful, the results will potentially have implications for athletic trainers, physiotherapists, and health care practitioners.

Trial registration
IRCT Iranian Registry of Clinical Trials IRCT20210927052616N1. Registered on November 03, 2021.