bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of continuous quality improvement in accreditation for medical education
Authors: Akdemir Nesibe , Peterson Linda N. , Campbell Craig M. , Scheele Fedde 
Published: September 2020

Abstract
Background
Accreditation systems are based on a number of principles and purposes that vary across jurisdictions. Decision making about accreditation governance suffers from a paucity of evidence. This paper evaluates the pros and cons of continuous quality improvement (CQI) within educational institutions that have traditionally been accredited based on episodic evaluation by external reviewers.

Methods
A naturalistic utility-focused evaluation was performed. Seven criteria, each relevant to government oversight, were used to evaluate the pros and cons of the use of CQI in three medical school accreditation systems across the continuum of medical education. The authors, all involved in the governance of accreditation, iteratively discussed CQI in their medical education contexts in light of the seven criteria until consensus was reached about general patterns.

Results
Because institutional CQI makes use of early warning systems, it may enhance the reflective function of accreditation. In the three medical accreditation systems examined, external accreditors lacked the ability to respond quickly to local events or societal developments. There is a potential role for CQI in safeguarding the public interest. Moreover, the central governance structure of accreditation may benefit from decentralized CQI. However, CQI has weaknesses with respect to impartiality, independence, and public accountability, as well as with the ability to balance expectations with capacity.

Conclusion
CQI, as evaluated with the seven criteria of oversight, has pros and cons. Its use still depends on the balance between the expected positive effects—especially increased reflection and faster response to important issues—versus the potential impediments. A toxic culture that affects impartiality and independence, as well as the need to invest in bureaucratic systems may make in impractical for some institutions to undertake CQI.
Responsiveness to societal needs in postgraduate medical education: the role of accreditation
Authors: Philibert Ingrid , Blouin Danielle 
Published: September 2020

Abstract
Background
Social accountability in medical education has been defined as an obligation to direct education, research, and service activities toward the most important health concerns of communities, regions, and nations. Drawing from the results of a summit of international experts on postgraduate medical education and accreditation, we highlight the importance of local contexts in meeting societal aims and present different approaches to ensuring societal input into medical education systems around the globe.

Main text
We describe four priorities for social responsiveness that postgraduate medical education needs to address in local and regional contexts: (1) optimizing the size, specialty mix, and geographic distribution of the physician workforce; (2) ensuring graduates’ competence in meeting societal goals for health care, population health, and sustainability; (3) promoting a diverse physician workforce and equitable access to graduate medical education; and (4) ensuring a safe and supportive learning environment that promotes the professional development of physicians along with safe and effective patient care in settings where trainees participate in care. We relate these priorities to the values proposed by the World Health Organization for social accountability: relevance, quality, cost-effectiveness, and equity; discuss accreditation as a lever for change; and describe existing and evolving efforts to make postgraduate medical education socially responsive.

Conclusion
Achieving social responsiveness in a competency-based postgraduate medical education system requires accrediting organizations to ensure that learning emphasizes relevant competencies in postgraduate curricula and educational experiences, and that graduates possess desired attributes. At the same time, institutions sponsoring graduate medical education need to provide safe and effective patient care, along with a supportive learning and working environment.
Grading reflective essays: the reliability of a newly developed tool- GRE-9
Authors: Makarem Nisrine N. , Saab Basem R. , Maalouf Grace , Musharafieh Umayya , Naji Fadila , Rahme Diana , Brome Dayana 
Published: September 2020

Abstract
Background
The main objective of this study is the development of a short reliable easy-to-use assessment tool in the aim of providing feedback to the reflective writings of medical students and residents.

Methods
This study took place in a major tertiary academic medical center in Beirut, Lebanon. Seventy-seven reflective essays written by 18 residents in the department of Family Medicine at the American University of Beirut Medical Center (AUBMC) were graded by 3 raters using the newly developed scale to assess the scale reliability. Following a comprehensive search and analysis of the literature, and based on their experience in reflective grading, the authors developed a concise 9-item scale to grade reflective essays through repeated cycles of development and analysis as well as the determination of the inter-rater reliability (IRR) using intra-class correlation coefficients (ICC) and Krippendorff’s Alpha.

Results
The inter-rater reliability of the new scale ranges from moderate to substantial with ICC of 0.78, 95% CI 0.64–0.86, p < 0.01 and Krippendorff’s Alpha was 0.49.

Conclusions
The newly developed scale, GRE-9, is a short, concise, easy-to-use reliable grading tool for reflective essays that has demonstrated moderate to substantial inter-rater reliability. This will enable raters to objectively grade reflective essays and provide informed feedback to residents and students.
Which factors are related to Finnish home care workers’ job satisfaction, stress, psychological distress and perceived quality of care? - a mixed method study
Authors: Ruotsalainen Salla , Jantunen Sami , Sinervo Timo 
Published: September 2020

Abstract
Background
The desire to increase the role of home care in Finland has created problems in home care work. Working conditions have deteriorated, the quality of care experienced is low, and staff members suffer from time pressure and stress, amongst other things. The aim of this article is to explore the challenges, stressors, teamwork and management factors that are associated with home care staff members’ well-being, job satisfaction and experienced care quality, and further, how staff members experience their work.

Methods
A survey was sent to home care workers in two case organizations that participated in the study. In addition, semi-structured theme interviews with home care workers were conducted. The data from the survey was analysed using analysis of covariance, and interview data was analysed using the Grounded Theory-based method from Gioia et al.

Results
Respondents of the survey and the interview participants were mainly female practical nurses. The results from the survey showed, for example, that time pressure was associated with higher stress and psychological distress, and interruptions were associated with lower job satisfaction and higher stress. In addition, variables related to teamwork, such as participative safety, were shown to explain the variation in quality of care. The analysis of the interview data further brought up dissatisfaction with management practices, which seems to have led to a decrease in job satisfaction. Exhaustion and strain were present among staff members, which originated from an insufficient number of carers.

Conclusions
Current working conditions and work practices in Finnish home care are experienced stressful. The results from this study indicate that having more autonomy at work was associated with job satisfaction, according to both analyses. Team climate and idea implementation were related to quality of care. Therefore, increasing self-organizing team practices might be a possible development method for improving working conditions and staff members’ well-being. Implementing self-organizing team practices could possibly also attract employees to work in home care and prevent turnover.
Functional signatures of evolutionarily young CTCF binding sites
Authors: Azazi Dhoyazan , Mudge Jonathan M. , Odom Duncan T. , Flicek Paul 
Published: September 2020

Abstract
Background
The introduction of novel CTCF binding sites in gene regulatory regions in the rodent lineage is partly the effect of transposable element expansion, particularly in the murine lineage. The exact mechanism and functional impact of evolutionarily novel CTCF binding sites are not yet fully understood. We investigated the impact of novel subspecies-specific CTCF binding sites in two Mus genus subspecies, Mus musculus domesticus and Mus musculus castaneus, that diverged 0.5 million years ago.

Results
CTCF binding site evolution is influenced by the action of the B2-B4 family of transposable elements independently in both lineages, leading to the proliferation of novel CTCF binding sites. A subset of evolutionarily young sites may harbour transcriptional functionality as evidenced by the stability of their binding across multiple tissues in M. musculus domesticus (BL6), while overall the distance of subspecies-specific CTCF binding to the nearest transcription start sites and/or topologically associated domains (TADs) is largely similar to musculus-common CTCF sites. Remarkably, we discovered a recurrent regulatory architecture consisting of a CTCF binding site and an interferon gene that appears to have been tandemly duplicated to create a 15-gene cluster on chromosome 4, thus forming a novel BL6 specific immune locus in which CTCF may play a regulatory role.

Conclusions
Our results demonstrate that thousands of CTCF binding sites show multiple functional signatures rapidly after incorporation into the genome.
Inhibition of αvβ3 integrin impairs adhesion and uptake of tumor-derived small extracellular vesicles
Authors: Altei Wanessa F. , Pachane Bianca C. , dos Santos Patty K. , Ribeiro Lígia N. M. , Sung Bong Hwan , Weaver Alissa M. , Selistre-de-Araújo Heloisa S. 
Published: September 2020

Abstract
Background
Extracellular vesicles (EVs) are lipid-bound particles that are naturally released from cells and mediate cell-cell communication. Integrin adhesion receptors are enriched in small EVs (SEVs) and SEV-carried integrins have been shown to promote cancer cell migration and to mediate organ-specific metastasis; however, how integrins mediate these effects is not entirely clear and could represent a combination of EV binding to extracellular matrix and cells.

Methods
To probe integrin role in EVs binding and uptake, we employed a disintegrin inhibitor (DisBa-01) of integrin binding with specificity for αvβ3 integrin. EVs were purified from MDA-MB-231 cells conditioned media by serial centrifugation method. Isolated EVs were characterized by different techniques and further employed in adhesion, uptake and co-culture experiments.

Results
We find that SEVs secreted from MDA-MB-231 breast cancer cells carry αvβ3 integrin and bind directly to fibronectin-coated plates, which is inhibited by DisBa-01. SEV coating on tissue culture plates also induces adhesion of MDA-MB-231 cells, which is inhibited by DisBa-01 treatment. Analysis of EV uptake and interchange between cells reveals that the amount of CD63-positive EVs delivered from malignant MDA-MB-231 breast cells to non-malignant MCF10A breast epithelial cells is reduced by DisBa-01 treatment. Inhibition of αvβ3 integrin decreases CD63 expression in cancer cells suggesting an effect on SEV content.

Conclusion
In summary, our findings demonstrate for the first time a key role of αvβ3 integrin in cell-cell communication through SEVs.

Graphical abstract
The Implementation Research Logic Model: a method for planning, executing, reporting, and synthesizing implementation projects
Authors: Smith Justin D. , Li Dennis H. , Rafferty Miriam R. 
Published: September 2020

Abstract
Background
Numerous models, frameworks, and theories exist for specific aspects of implementation research, including for determinants, strategies, and outcomes. However, implementation research projects often fail to provide a coherent rationale or justification for how these aspects are selected and tested in relation to one another. Despite this need to better specify the conceptual linkages between the core elements involved in projects, few tools or methods have been developed to aid in this task. The Implementation Research Logic Model (IRLM) was created for this purpose and to enhance the rigor and transparency of describing the often-complex processes of improving the adoption of evidence-based interventions in healthcare delivery systems.

Methods
The IRLM structure and guiding principles were developed through a series of preliminary activities with multiple investigators representing diverse implementation research projects in terms of contexts, research designs, and implementation strategies being evaluated. The utility of the IRLM was evaluated in the course of a 2-day training to over 130 implementation researchers and healthcare delivery system partners.

Results
Preliminary work with the IRLM produced a core structure and multiple variations for common implementation research designs and situations, as well as guiding principles and suggestions for use. Results of the survey indicated a high utility of the IRLM for multiple purposes, such as improving rigor and reproducibility of projects; serving as a “roadmap” for how the project is to be carried out; clearly reporting and specifying how the project is to be conducted; and understanding the connections between determinants, strategies, mechanisms, and outcomes for their project.

Conclusions
The IRLM is a semi-structured, principle-guided tool designed to improve the specification, rigor, reproducibility, and testable causal pathways involved in implementation research projects. The IRLM can also aid implementation researchers and implementation partners in the planning and execution of practice change initiatives. Adaptation and refinement of the IRLM are ongoing, as is the development of resources for use and applications to diverse projects, to address the challenges of this complex scientific field.
Prevalence, mortality and healthcare economic burden of tuberous sclerosis in Hong Kong: a population-based retrospective cohort study (1995–2018)
Authors: Chu William Ching-Yuen , Chiang Lorraine Lok-Wing , Chan Dorothy Chi-Ching , Wong Wilfred Hing-Sang , Chan Godfrey Chi-Fung 
Published: September 2020

Abstract
Background
We aim to elucidate the disease impact by accounting the prevalence, survival rate, genetics, mTOR inhibitor use and direct costs of tuberous sclerosis complex (TSC) in our local setting. TSC patients with documented visits to our local public hospitals in 1995–2018 were identified. The public hospitals captured most if not all local TSC patients. Demographics such as age, sex, death, genetic profiles were retrieved from the central electronic database. Data including prevalence, age distribution and survival rate were analysed. Direct cost was calculated with reference to the drug use and number of visits to various public hospital facilities.

Results
We identified 284 surviving TSC patients (55.3% male) in Hong Kong. The age range was from 4.5 months to 89.9 years, with a median age of 27.2 years. Paediatrics (< 18 years) to adult (≥18 years) ratio was 1:2.84. The overall prevalence of TSC patients was 3.87 in 100,000 (i.e. 1 in 25,833). Genetically, TSC1:TSC2 ratio is 1:2.7.
Thirty seven patients died within the study period. The age of death ranged from 7.6 years to 77.8 years, with a median age of death at 36.6 years (IQR: 24.7–51.1 years). Most patients survived till adulthood. Survival rate at 20 and 50 years follow-up was 98.6 and 79.5% respectively.
Two hundred and twenty nine TSC patients (71.3%) had neurological manifestations, sixteen patients (5.0%) had chronic kidney diseases and five patients (1.6%) had pulmonary lymphangioleiomyomatosis. Forty seven (16.5%) TSC patients were prescribed with mTOR inhibitors within the study period. Healthcare facility utilization was further analysed in the 2008–2018 cohort. In particular, the mean number of specialist out-patient clinic visits per patient-year was 9.23 per patient-year, which was 4.91 times more than that of local general population.

Conclusions
Prevalence of local TSC patients is within the range of that reported in the literature. Local TSC patients have fair long term survival, but they require disproportionally high healthcare cost when compared with the general population, particularly in terms of outpatient (OP) visits. Although effective disease-modifying agent (i.e. mTOR inhibitor) is available, it was not widely used yet in Hong Kong despite the fact that Government approved and supported its use recently. Further research on quality of life and setting up a comprehensive patient registry are necessary for more accurate assessment of cost and benefit.
Small-molecule MMP2/MMP9 inhibitor SB-3CT modulates tumor immune surveillance by regulating PD-L1
Authors: Ye Youqiong , Kuang Xinwei , Xie Zuozhong , Liang Long , Zhang Zhao , Zhang Yongchang , Ma Fangyu , Gao Qian , Chang Ruimin , Lee Heng-Huan , Zhao Shuang , Su Juan , Li Hui , Peng Jingbo , Chen Huifang , Yin Minzhu , Peng Cong , Yang Nong , Wang Jing , Liu Jing , Liu Hong , Han Leng , Chen Xiang 
Published: September 2020

AbstractBackgroundImmune checkpoint blockade (ICB) therapy has demonstrated considerable clinical benefit in several malignancies, but has shown favorable response in only a small proportion of cancer patients. Recent studies have shown that matrix metalloproteinases (MMPs) are highly associated with the microenvironment of tumors and immune cells. However, it is unknown whether MMPs are involved in immunotherapy.MethodsHere, we used integrative analysis to explore the expression landscape of the MMP family and its association with immune features across multiple cancer types. We used T cell cytotoxicity-mediated tumor killing assay to determine the co-cultured T cell activity of SB-3CT, an MMP2/9 inhibitor. We then used in vitro assays to examine the regulating roles of SB-3CT on PD-L1. We further characterized the efficacy of SB-3CT, in combination with anti-PD-1 and/or anti-CTLA4 treatment in mouse models with melanoma and lung cancer.ResultsOur computational analysis demonstrated a strong association between MMP2/9 and immune features. We demonstrated that inhibition of MMP2/9 by SB-3CT significantly reduced the tumor burden and improved survival time by promoting anti-tumor immunity. Mechanistically, we showed that SB-3CT treatment significantly diminished both mRNA and protein levels of PD-L1 in cancer cells. Pre-clinically, SB-3CT treatment enhanced the therapeutic efficacy of PD-1 or CTLA-4 blockade in the treatment of both primary and metastatic tumors.ConclusionsOur study unraveled novel molecular mechanisms regarding the regulation of tumor PD-L1 and provided a novel combination therapeutic strategy of SB-3CT and ICB therapy to enhance the efficacy of immunotherapy.
Evaluation of bacterial diversity during fermentation process: a comparison between handmade and machine-made high-temperature Daqu of Maotai-flavor liquor
Authors: Zuo Qiancheng , Huang Yongguang , MinGuo  
Published: September 2020

Abstract
Purpose
High-temperature Daqu is a traditional fermentation starter that is used for Chinese Maotai-flavor Baijiu production. Although the bacteria in high-temperature Daqu are known to be responsible for developing the quality and flavor of Baijiu during the fermentation process, there is little information on the properties of the bacteria during the fermentation of high-temperature Daqu, especially machine-made high-temperature Daqu. This has limited the development of the Maotai-flavor Baijiu industry, particularly with regard to the mechanized production of Maotai-flavor Baijiu.

Methods
Illumina MiSeq high-throughput sequencing was applied to study bacterial compositions during the fermentation of handmade and machine-made high temperatures.

Results
The results show that bacterial diversity in machine-made Daqu was similar but higher than that in handmade Daqu at the end of fermentation, and there was no significant difference between the methods with regard to the dominant genera and their dynamic changes during fermentation. Rhizobium, Bacillus, Thermoactinomyces, Weissella, Lactobacillus, and Saccharopolyspora were the dominant genera during the fermentation of both Daqus, although the relative abundance of these dominant genera differed between the two methods. Interestingly, the machine-made Daqu contained a higher relative abundance of Bacillus than handmade Daqu at all fermentation times. Bacillus is the most important functional bacteria in the fermentation of Maotai-flavor Baijiu, suggesting that mechanical-molding methods could be applied to industrial Maotai-flavor Daqu production.

Conclusion
These results suggest that mechanical-molding methods could be applied to industrial Maotai-flavor Daqu production, which could be helpful for industrial Maotai-flavor Baijiu production and the development of fermentation technology.
Optical mapping of human embryonic stem cell-derived cardiomyocyte graft electrical activity in injured hearts
Authors: Filice Dominic , Dhahri Wahiba , Solan Joell L. , Lampe Paul D. , Steele Erin , Milani Nikita , Van Biber Benjamin , Zhu Wei-Zhong , Valdman Tamilla Sadikov , Romagnuolo Rocco , Otero-Cruz José David , Hauch Kip D. , Kay Matthew W. , Sarvazyan Narine , Laflamme Michael A. 
Published: September 2020

Abstract
Background
Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) show tremendous promise for cardiac regeneration, but the successful development of hESC-CM-based therapies requires improved tools to investigate their electrical behavior in recipient hearts. While optical voltage mapping is a powerful technique for studying myocardial electrical activity ex vivo, we have previously shown that intra-cardiac hESC-CM grafts are not labeled by conventional voltage-sensitive fluorescent dyes. We hypothesized that the water-soluble voltage-sensitive dye di-2-ANEPEQ would label engrafted hESC-CMs and thereby facilitate characterization of graft electrical function and integration.

Methods
We developed and validated a novel optical voltage mapping strategy based on the simultaneous imaging of the calcium-sensitive fluorescent protein GCaMP3, a graft-autonomous reporter of graft activation, and optical action potentials (oAPs) derived from di-2-ANEPEQ, which labels both graft and host myocardium. Cardiomyocytes from three different GCaMP3+ hESC lines (H7, RUES2, or ESI-17) were transplanted into guinea pig models of subacute and chronic infarction, followed by optical mapping at 2 weeks post-transplantation.

Results
Use of a water-soluble voltage-sensitive dye revealed pro-arrhythmic properties of GCaMP3+ hESC-CM grafts from all three lines including slow conduction velocity, incomplete host-graft coupling, and spatially heterogeneous patterns of activation that varied beat-to-beat. GCaMP3+ hESC-CMs from the RUES2 and ESI-17 lines both showed prolonged oAP durations both in vitro and in vivo. Although hESC-CMs partially remuscularize the injured hearts, histological evaluation revealed immature graft structure and impaired gap junction expression at this early timepoint.

Conclusion
Simultaneous imaging of GCaMP3 and di-2-ANEPEQ allowed us to acquire the first unambiguously graft-derived oAPs from hESC-CM-engrafted hearts and yielded critical insights into their arrhythmogenic potential and line-to-line variation.