bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring trends in admissions and treatment for ankle fractures: a longitudinal cohort study of routinely collected hospital data in England
Authors: Scott Lauren J. , Jones Tim , Whitehouse Michael R. , Robinson Peter W. , Hollingworth William 
Published: August 2020

Abstract
Background
Evidence on the most effective and cost-effective management of ankle fractures is sparse but evolving. A recent large RCT in older patients with unstable fractures found that management with close-contact-casting was functionally equivalent and more cost-effective than internal fixation. We describe temporal and geographic variation in ankle fracture management and estimate the potential savings if close-contact-casting was used more often in older patients.

Methods
Patients admitted to hospital in England between 2007/08 and 2016/17 with an ankle fracture were identified using routine hospital episode statistics. We tested whether the use of internal fixation, and the proportion of internal fixations using intramedullary implants, changed over time. We estimated the potential annual cost savings if patients aged 60+ years were treated with close-contact-casting rather than internal fixation, in line with emerging evidence.

Results
Over the 10-year period, there were 223,465 hospital admissions with a primary ankle fracture diagnosis. The incidence (per 100,000) of internal fixation was fairly consistent over time in younger (33.2 in 2007/08, 30.9 in 2016/17) and older (36.5 in 2007/08, 37.4 in 2016/17) patients. The proportion of internal fixations which used intramedullary implants increased in both age groups (17.0–19.5% < 60 years; 15.2–17.4% 60+ years). In 2016/17, the cost of inpatient hospital care for ankle fractures in England was over £63.1million. If 50% of older patients who had an internal fixation instead had close-contact-casting, we estimate that approximately £1.56million could have been saved.

Conclusions
Despite emerging evidence that non-surgical and surgical management achieve equivalent functional outcomes in older patients, the rate of surgical fixation has remained relatively stable over the decade. The health service could achieve substantial savings if a higher proportion of older patients were treated with close-contact-casting, in line with recent evidence.
Precise base editing with CC context-specificity using engineered human APOBEC3G-nCas9 fusions
Authors: Liu Zhiquan , Chen Siyu , Shan Huanhuan , Jia Yingqi , Chen Mao , Song Yuning , Lai Liangxue , Li Zhanjun 
Published: August 2020

AbstractBackgroundCytidine base editors (CBEs), composed of a cytidine deaminase fused to Cas9 nickase (nCas9), enable efficient C-to-T conversion in various organisms. However, current base editors can induce unwanted bystander C-to-T conversions when multiple Cs are present in the ~ 5-nucleotide activity window of cytidine deaminase, which negatively affects their precision. Here, we develop a new base editor which significantly reduces unwanted bystander activities.ResultsWe used an engineered human APOBEC3G (eA3G) C-terminal catalytic domain with preferential cytidine-deaminase activity in motifs with a hierarchy CCC>CCC>CC(where the preferentially deaminated C is underlined), to develop an eA3G-BE with distinctive CCcontext-specificity and reduced generation of bystander mutations. Targeted editing efficiencies of 18.3–58.0% and 54.5–92.2% with excellent CCcontext-specificity were generated in human cells and rabbit embryos, respectively. In addition, a base editor that can further recognize relaxed NG PAMs is achieved by combining hA3G with an engineered SpCas9-NG variant. The A3G-BEs were used to induce accurate single-base substitutions which led to nonsense mutation with an efficiency of 83–100% and few bystander mutations in Founder (F0) rabbits atTyrloci.ConclusionsThese novel base editors with improved precision and CCcontext-specificity will expand the toolset for precise gene modification in organisms.
The mTOR/ULK1 signaling pathway mediates the autophagy-promoting and osteogenic effects of dicalcium silicate nanoparticles
Authors: Ruolan Wang , Liangjiao Chen , Longquan Shao 
Published: August 2020

AbstractA novel bioactive inorganic material containing silicon, calcium and oxygen, calcium silicate (Ca2SiO4, C2S) with a CaO-SiO2 ingredient, has been identified as a potential candidate for artificial bone. Autophagy has an essential function in adult tissue homoeostasis and tumorigenesis. However, little is known about whether silicate nanoparticles (C2S NPs) promote osteoblastic differentiation by inducing autophagy. Here we investigated the effects of C2S NPs on bone marrow mesenchymal stem cell differentiation (BMSCs) in osteoblasts. Furthermore, we identified the osteogenic gene and protein expression in BMSCs treated with C2S NPs. We found that autophagy is important for the ability of C2S NPs to induce osteoblastic differentiation of BMSCs. Our results showed that treatment with C2S NPs upregulated the expression of BMP2, UNX2, and OSX in BMSCs, and significantly promoted the expression of LC3 and Beclin, while P62 (an autophagy substrate) was downregulated. C2S NP treatment could also enhance Alizarin red S dye (ARS), although alkaline phosphatase (ALP) activity was not significantly changed. However, all these effects could be partially reversed by 3-MA. We then detected potential signaling pathways involved in this biological effect and found that C2S NPs could activate autophagy by suppressing mTOR and facilitating ULK1 expression. Autophagy further activated β-catenin expression and promoted osteogenic differentiation. In conclusion, C2S NPs promote bone formation and osteogenic differentiation in BMSCs by activating autophagy. They achieve this effect by activating mTOR/ULK1, inducing autophagy, and subsequently triggering the WNT/β-catenin pathway to boost the differentiation and biomineralization of osteoblasts.
Novel design of (PEG-ylated)PAMAM-based nanoparticles for sustained delivery of BDNF to neurotoxin-injured differentiated neuroblastoma cells
Authors: Dąbkowska Maria , Łuczkowska Karolina , Rogińska Dorota , Sobuś Anna , Wasilewska Monika , Ulańczyk Zofia , Machaliński Bogusław 
Published: August 2020

AbstractBrain-derived neurotrophic factor (BDNF) is essential for the development and function of human neurons, therefore it is a promising target for neurodegenerative disorders treatment. Here, we studied BDNF-based electrostatic complex with dendrimer nanoparticles encapsulated in polyethylene glycol (PEG) in neurotoxin-treated, differentiated neuroblastoma SH-SY5Y cells, a model of neurodegenerative mechanisms. PEG layer was adsorbed at dendrimer-protein core nanoparticles to decrease their cellular uptake and to reduce BDNF-other proteins interactions for a prolonged time. Cytotoxicity and confocal microscopy analysis revealed PEG-ylated BDNF-dendrimer nanoparticles can be used for continuous neurotrophic factor delivery to the neurotoxin-treated cells over 24 h without toxic effect. We offer a reliable electrostatic route for efficient encapsulation and controlled transport of fragile therapeutic proteins without any covalent cross-linker; this could be considered as a safe drug delivery system. Understanding the polyvalent BDNF interactions with dendrimer core nanoparticles offers new possibilities for design of well-ordered protein drug delivery systems.
Further development in the assessment of psychological flexibility: validation of the German committed action questionnaire
Authors: Terhorst Yannik , Baumeister Harald , McCracken Lance M. , Lin Jiaxi 
Published: August 2020

Abstract
Background
Psychological flexibility is considered a fundamental aspect of health. It includes six interrelated facets: 1) cognitive defusion, 2) acceptance, 3) contact with the present moment, 4) self-as-context, 5) values, and 6) committed action. To gain further insight into psychological flexibility and its effects on health, reliable and valid instruments to assess all facets are needed. Committed action is one facet that is understudied. A long and short version of a validated measure (CAQ and CAQ-8) have been developed in English. Currently, there are no German versions of the CAQ. Aim of this study is to validate German-language versions of these in a chronic pain population.

Methods
The CAQ instructions and items were translated and evaluated in a chronic pain population (N = 181). Confirmatory factor analysis and Mokken scale analysis were conducted to evaluate the German questionnaires. Correlations with health outcomes, including quality of life (SF-12), physical and emotional functioning (MPI, BPI, PHQ-9, GAD-7), pain intensity, and with other facets of psychological flexibility (CPAQ, FAH-II) were investigated for convergent validity purposes. Scale reliability was assessed by the alpha, MS, lambda-2, LCRC, and omega coefficient.

Results
A bifactor model consisting of one general factor and two methodological factors emerged from the analysis. Criteria for reliability and validity were met. Medium to strong correlations to health outcomes and other facets of psychological flexibility were found. Results were similar to the original English version.

Conclusions
The present study presents a valid and reliable instrument to investigate committed action in German populations. Future studies could expand the present findings by evaluating the German CAQ versions in non-pain populations. The role of committed action and the wider psychological flexibility model in pain and other conditions deserves further investigation.
Burden of Care in Caregivers of Iranian patients with chronic disorders: a systematic review and meta-analysis
Authors: Rezaei Hayedeh , Niksima Seyed Hassan , Ghanei Gheshlagh Reza 
Published: August 2020

Abstract
Introduction
Caring for patients with chronic disorders can lead to different problems for caregivers in physical, psychological, social, family, and financial domains. High levels of burden of care can make caregivers vulnerable to physical and psychological conditions and influence their quality of life. Therefore, the goal of the present study was to estimate the overall percentage of burden of care in caregivers of Iranian patients with chronic disorders.

Methods
A total of 25 articles published from inception to February 2019 were reviewed. Search for articles was conducted in international (Scopus, Web of Science, and PubMed) and domestic (Scientific Information Database (SID) and MagIran) databases, using the following keywords: “Caregiver,” “Burden,” and “Iran,” and their possible combinations. The data were analyzed using the meta-analysis method and the random effects model. All the analyses were performed using STATA, version 14.

Results
The overall percentage of burden of care in caregivers of Iranian patients with chronic disorders was 53.28% (95% CI: 46.13–60.43). The highest percentage of burden of care was related to dialysis (62.75; 95% CI: 56.11–69.38), mental disorders (58.69; 95% CI: 49.70–67.69), and Alzheimer’s disease (57.07; 95% CI: 46.23–67.92), respectively; and the lowest percentage of burden of care was related to diabetes (34.92; 95% CI: 18.01–51.82).

Conclusions
Caregivers of Iranian patients with chronic disorders experience high levels of burden of care, especially those caring for patients undergoing dialysis, patients with mental disorders, and patients with Alzheimer’s disease. Therefore, necessary measures need to be taken by Iranian health care officials to reduce burden of care in caregivers.
The impact of health literacy on college students’ psychological disturbances and quality of life: a structural equation modeling analysis
Authors: Rababah Jehad A. , Al-Hammouri Mohammed M. , Drew Barbara L. 
Published: August 2020

Abstract
Background
The literature regarding the effect of health literacy on college students’ psychological health and quality of life is scarce. The purpose of conducting this cross-sectional study was to examine the effect of health literacy on certain psychological disturbances (perceived stress, depressive symptoms, and impulsivity) and quality of life of college students.

Methods
A cross-sectional quantitative design was utilized in this study. A total of 310 four-year college students participated in this study. The students completed a demographics questionnaire as well as already established and validated measures of health literacy, perceived stress, depressive symptoms, impulsivity, and quality of life. Structural equation modeling was performed to analyze the data to explore the effect of health literacy on the psychological disturbances and quality of life.

Results
The results showed that health literacy has a negative effect on three psychological disturbances commonly experienced by college students; perceived stress, depressive symptoms, and impulsivity. In addition, the effect of health literacy on the quality of life was positive.

Conclusion
The proposed conceptual model was supported. College students’ counseling staff could use the findings to better address students’ needs pertinent to psychological health and quality of life. Future research is warranted to develop a more comprehensive model that explains the role of health literacy in determining college students’ psychological health and quality of life.
The treatment strategy of R0 resection in colorectal cancer with synchronous para-aortic lymph node metastasis
Authors: Ushigome Hajime , Yasui Masayoshi , Ohue Masayuki , Haraguchi Naoaki , Nishimura Junichi , Sugimura Keijirou , Yamamoto Kazuyoshi , Wada Hiroshi , Takahashi Hidenori , Omori Takeshi , Miyata Hiroshi , Takiguchi Shuji 
Published: August 2020

Abstract
Background
Synchronous metastatic para-aortic lymph node (mPALN) dissectionin colorectal cancer has relatively good oncological outcomes, though many patients develop recurrence. Universal prognostic factor remain unclear and no definitive perioperative chemotherapy is available, making the treatment of mPALN controversial. In the present study, we aimed to establish a treatment strategy for synchronous mPALN.

Methods
This retrospective study involved 20 patients with pathological mPALN below the renal vein who underwent R0 resection. Long-term outcomes, recurrence type, and prognostic factors for survival were investigated.

Results
The 5-year overall survival and recurrence-free survival rates were 39% and 25%, respectively. Seventeen patients (85%) developed recurrence, including 13 (76%) within 1 year after surgery, and ~ 70% of all recurrences were multiple recurrences. Four patients (20%) survived > 5 years. Pathological T stage (p= 0.011), time to recurrence (p = 0.007), and recurrence resection (p = 0.009) were identified as prognostic factors for long-term survival.

Conclusions
R0 resection of synchronous mPALN in colorectal cancer resulted in acceptable oncological outcomes, though we found a high rate of early unresectable recurrence. If the recurrence occurs late or isolated, surgical resection should be considered for longer survival.
Communities of practice in Alberta Health Services: advancing a learning organisation
Authors: Auer Anna M. , Hanson Patricia , Brady-Fryer Barbara , Alati-it Julie , Johnson Allison L. 
Published: August 2020

AbstractBackgroundIn 2009, Alberta Health Services (AHS) became Canada’s first and largest fully integrated healthcare system, involving the amalgamation of nine regional health authorities and three provincial services. Within AHS, communities of practice (CoPs) meet regularly to learn from one another and to find ways to improve service quality. This qualitative study examined CoPs as an applied practice of a learning organisation along with their potential influence in a healthcare system by exploring the perspectives of CoP participants.MethodsA collective case study method was used to enable the examination of a cross-section of cases in the study organisation. Semi-structured interviews were conducted with 31 participants representing 28 distinct CoPs. Using Senge’s framework of a learning organisation, CoP influences associated with team learning and organisational change were explored.ResultsCoPs in AHS were described as diverse in practice domains, focus, membership boundaries, attendance and sphere of influence. Using small-scale resource investments, CoPs provided members with opportunities for meaningful interactions, the capacity to build information pathways, and enhanced abilities to address needs at the point of care and service delivery. Overall, CoPs delivered a sophisticated array of engagement and knowledge-sharing activities perceived as supportive of organisational change, systems thinking, and the team learning practice critical to a learning organisation.ConclusionCoPs enable the diverse wealth of knowledge embedded in people, local conditions and special circumstances to flow from practice domain groups to programme and service areas, and into the larger system where it can effect organisational change. This research highlights the potential of CoPs to influence practice and broad-scale change more directly than previously understood or reported in the literature. As such, this study suggests that CoPs have the potential to influence and advance widespread systems change in Canadian healthcare.
The cross-sectional average length of healthy life (HCAL): a measure that summarizes the history of cohort health and mortality
Authors: Sauerberg Markus , Guillot Michel , Luy Marc 
Published: August 2020

AbstractBackgroundHealthy life years have superseded life expectancy (LE) as the most important indicator for population health. The most common approach to separate the total number of life years into those spent in good and poor health is the Sullivan method which incorporates the health dimension to the classic period life table, thus transforming the LE indicator into the health expectancy (HE) indicator. However, life years derived from a period life table and health prevalence derived from survey data are based on different conceptual frameworks.MethodWe modify the Sullivan method by combining the health prevalence data with the conceptually better fitting cross-sectional average length of life (CAL). We refer to this alternative HE indicator as the “cross-sectional average length of healthy life” (HCAL). We compare results from this alternative indicator with the conventional Sullivan approach for nine European countries. The analyses are based on EU-SILC data in three empirical applications, including the absolute and relative level of healthy life years, changes between 2008 and 2014, and the extent of the gender gap.ResultsHCAL and conventional HE differ in each of these empirical applications. In general, HCAL provides larger gains in healthy life years in recent years, but at the same time greater declines in the proportion of healthy life years. Regarding the gender gap, HCAL provides a more favourable picture for women compared to conventional HE. Nonetheless, the extent of these differences between the indicators is only of minor extent.ConclusionsAlbeit the differences between HE and HCAL are small, we found some empirical examples in which the two indicators led to different conclusions. It is important to note, however, that the measurement of health and the data quality are much more important for the healthy life years indicator than the choice of the variant of the Sullivan method. Nonetheless, we suggest to use HCAL in addition to HE whenever possible because it widens the spectrum of empirical analyses and serves for verification of results based on the highly sensitive HE indicator.
The crosstalk: exosomes and lipid metabolism
Authors: Wang Wei , Zhu Neng , Yan Tao , Shi Ya-Ning , Chen Jing , Zhang Chan-Juan , Xie Xue-Jiao , Liao Duan-Fang , Qin Li 
Published: August 2020

AbstractExosomes have been considered as novel and potent vehicles of intercellular communication, instead of “cell dust”. Exosomes are consistent with anucleate cells, and organelles with lipid bilayer consisting of the proteins and abundant lipid, enhancing their “rigidity” and “flexibility”. Neighboring cells or distant cells are capable of exchanging genetic or metabolic information via exosomes binding to recipient cell and releasing bioactive molecules, such as lipids, proteins, and nucleic acids. Of note, exosomes exert the remarkable effects on lipid metabolism, including the synthesis, transportation and degradation of the lipid. The disorder of lipid metabolism mediated by exosomes leads to the occurrence and progression of diseases, such as atherosclerosis, cancer, non-alcoholic fatty liver disease (NAFLD), obesity and Alzheimer’s diseases and so on. More importantly, lipid metabolism can also affect the production and secretion of exosomes, as well as interactions with the recipient cells. Therefore, exosomes may be applied as effective targets for diagnosis and treatment of diseases.
AKT/FOXO1 axis links cross-talking of endothelial cell and pericyte in TIE2-mutated venous malformations
Authors: Si Yameng , Huang Jiadong , Li Xiang , Fu Yu , Xu Rongyao , Du Yifei , Cheng Jie , Jiang Hongbing 
Published: August 2020

AbstractBackgroundVenous malformations (VMs), most of which associated with activating mutations in the endothelial cells (ECs) tyrosine kinase receptor TIE2, are characterized by dilated and immature veins with scarce smooth muscle cells (SMCs) coverage. However, the underlying mechanism of interaction between ECs and SMCs responsible for VMs has not been fully understood.MethodsHere, we screened 5 patients with TIE2-L914F mutation who were diagnosed with VMs by SNP sequencing, and we compared the expression of platelet-derived growth factor beta (PDGFB) and α-SMA in TIE2 mutant veins and normal veins by immunohistochemistry. In vitro, we generated TIE2-L914F-expressing human umbilical vein endothelial cells (HUVECs) and performed BrdU, CCK-8, transwell and tube formation experiments on none-transfected and transfected ECs. Then we investigated the effects of rapamycin (RAPA) on cellular characteristics. Next we established a co-culture system and investigated the role of AKT/FOXO1/PDGFB in regulating cross-talking of mutant ECs and SMCs.ResultsVMs with TIE2-L914F mutation showed lower expression of PDGFB and α-SMA than normal veins. TIE2 mutant ECs revealed enhanced cell viability and motility, and decreased tube formation, whereas these phenotypes could be reversed by rapamycin. Mechanically, RAPA ameliorated the physiological function of mutant ECs by inhibiting AKT-mTOR pathway, but also facilitated the nuclear location of FOXO1 and the expression of PDGFB in mutant ECs, and then improved paracrine interactions between ECs and SMCs. Moreover, TIE2 mutant ECs strongly accelerated the transition of SMCs from contractile phenotype to synthetic phenotype, whereas RAPA could prevent the phenotype transition of SMCs.ConclusionsOur data demonstrate a previously unknown mechanistic linkage of AKT-mTOR/FOXO1 pathway between mutant ECs and SMCs in modulating venous dysmorphogenesis, and AKT/FOXO1 axis might be a potential therapeutic target for the recovery of TIE2-mutation causing VMs.Graphical abstract