bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of the opioid self-management scale for advanced Cancer patients with pain and examination of its validity and reliability
Authors: Yoshida Shiori , Sato Fumiko , Tagami Keita , Sasaki Rie , Takahashi Chikako , Sasaki Konosuke , Takahashi Shin 
Published: June 2022

Abstract
Background
Approximately 60% of outpatients with advanced cancer experience pain; therefore, self-management of opioid use is important for appropriate pain relief. To date, no studies have clearly described the concept of opioid self-management or assessed the factors involved, including the improvement of self-management abilities. This study developed, and evaluated the validity and reliability of an opioid self-management scale for advanced cancer patients with pain (OSSA). Opioid self-management in advanced cancer patients with pain was defined as the management of opioid medication performed by patients with advanced cancer to relieve cancer pain on their own.

Methods
Three phases were required for validation and reliability of the OSSA: 1) testing content validity, 2) testing face validity, and 3) testing construct validity, concurrent validity and reliability.

Results
After a three-phase process, the OSSA consisted of 33 items on six subscales. The structural equation modeling was such that the χ2 value was 709.8 (p < 0.001, df = 467), goodness-of-fit index was 0.78, adjusted goodness-of-fit index was 0.73, root mean squares of approximation was 0.063, and comparative fit index was 0.92. The Pearson correlation coefficients between the total OSSA score and the 24-hour average pain or pain relief over 24 hours were − 0.21 (p < 0.05) and 0.26 (p < 0.01), respectively. Cronbach’s α was 0.93. The intraclass correlation coefficient range was 0.59–0.90.

Conclusion
The findings of this study show that the OSSA has acceptable validity and reliability, and that better self-management leads to greater pain relief. The OSSA can be considered effective for use in research, but shortened version should be prepared for realistic and practical clinical use.
Impacts of early clinical exposure on undergraduate student professionalism—a qualitative study
Authors: Liu Chun-i , Tang Kung-pei , Wang Yun-chu , Chiu Chiung-hsuan 
Published: June 2022

Abstract
Introduction
Early clinical exposure (ECE), or authentic human contact in a social or clinical context during preclinical training, has been adopted by many medical schools. This study aims to investigate how medical students’ sense of professionalism changed after ECE intervention, with the aim of informing curriculum design to enhance student awareness of the importance of medical professionalism.

Method
Focus groups of ECE students were held to collect data for the study. All participants read interview guidelines before starting. During the focus groups, the students discussed their medical obligations as perceived throughout the course, which offered a choice between four different ECE tracks. They were then asked to report their understanding of the situations they encountered during the course and reflect on their implications.

Results
Six focus groups of 22 students in total from a medical school in northern Taiwan were held shortly after the students completed an ECE course in September 2019. From their responses, 10 categories relating to medical professionalism were deduced categorized under 5 major dimensions. An additional 8 sub-dimensions on attitudes and 2 sub-dimensions on personal well-being were also identified as new categories separate from but related to medical professionalism. After the ECE intervention, about 59% of participants redefined their understanding of medical professionalism.

Conclusion
ECE and intensive interaction with key stakeholders, including patients and their families, help students in the early stages of medical education form and cultivate a sense of medical professionalism. However, the relationship between participants’ personalities, motivations, and clinical activities requires further investigation.
Attitudes of home-visiting nurses toward risk management of patient safety incidents in Japan
Authors: Yoshimatsu Keiko , Nakatani Hisae 
Published: June 2022

Abstract
Background
In situations of home care, patients and their family members must address problems and emergencies themselves. For this reason, home-visiting nurses (HVNs) must practice risk management to ensure that patients can continue receiving care in the comfort of their homes. The purpose of this study was to examine HVNs’ attitudes toward risk management.

Methods
This study adopted a qualitative description approach. Semi-structured interviews were conducted to collect information on HVNs’ risk management behavior and their attitudes toward it. Participants comprised 11 HVNs working at home-visiting nursing agencies in a prefecture of Japan. Transcribed interviews were analyzed using content analysis.

Results
Nurses’ attitudes toward risk management comprised the following themes: (i) predicting and avoiding risks, (ii) ensuring medical safety in home settings, (iii) coping with incidents, and (iv) playing the role of administrators in medical safety, which was answered only by administrators.

Conclusions
When practicing risk management, home-visiting nurses should first assess the level of understanding of the patient and family, followed by developing safety measures tailored to their everyday needs. These results further suggest that administrators should take actions to foster a working environment conducive to risk management. These actions include coordinating duties to mitigate risk and improve the process of reporting risks. This study provides a baseline for future researchers to assist patients and families requiring medical care services of this nature.
Job demands, job resources, and health outcomes among nursing professionals in private and public healthcare sectors in Sweden – a prospective study
Authors: Thapa Dip Raj , Stengård Johanna , Ekström-Bergström Anette , Areskoug Josefsson Kristina , Krettek Alexandra , Nyberg Anna 
Published: June 2022

Abstract
Background
Nursing professionals exhibit high prevalence of stress-related health problems. Job demands and job resources are parallel drivers of health and well-being among employees. Better job resources associate with better job satisfaction, job motivation and engagement even when job demands are high. To date, there is limited research which explores the association between job demands, job resources and health outcomes among nursing professionals in the Swedish context. The aim of this study was therefore to investigate Swedish nursing professionals’ job demands and job resources in relation to health outcomes, with comparisons between the private and public healthcare sectors. The specific research questions were as follows: (1) Are there differences between private and public healthcare regarding job demands, job resources, and health outcomes? and (2) Are there prospective associations between job demands and job resources in relation to health outcomes?

Methods
Data were drawn from the Swedish Longitudinal Occupational Survey of Health (SLOSH) 2016 and 2018, including 520 nurses and 544 assistant nurses working in the private and public healthcare sectors from 2016 (baseline). Data were analyzed using binary logistic regression.

Results
Nursing professionals reported higher threats, lower bullying, lower control, lower social support, and lower cohesion in the public healthcare units compared to the private healthcare units. The prospective analyses showed that job resources in terms of social support and rewards were associated with higher self-rated health and lower burnout. Cohesion was associated with higher self-rated health. Job demands in terms of psychological demands and job efforts were associated with lower self-rated health, higher burnout, and higher sickness absence, while emotional demands were associated with higher burnout.

Conclusions
Nursing professionals’ job resources are deficient in public healthcare units. Job resources are associated with positive health outcomes, whereas job demands are associated with negative health outcomes, among nursing professionals. Strengthening job resources among nursing professionals in the private and public healthcare sectors can promote and sustain their work-related health.
Bioengineering in salivary gland regeneration
Authors: Hajiabbas Maryam , D’Agostino Claudia , Simińska-Stanny Julia , Tran Simon D. , Shavandi Amin , Delporte Christine 
Published: June 2022

AbstractSalivary gland (SG) dysfunction impairs the life quality of many patients, such as patients with radiation therapy for head and neck cancer and patients with Sjögren’s syndrome. Multiple SG engineering strategies have been considered for SG regeneration, repair, or whole organ replacement. An in-depth understanding of the development and differentiation of epithelial stem and progenitor cells niche during SG branching morphogenesis and signaling pathways involved in cell–cell communication constitute a prerequisite to the development of suitable bioengineering solutions. This review summarizes the essential bioengineering features to be considered to fabricate an engineered functional SG model using various cell types, biomaterials, active agents, and matrix fabrication methods. Furthermore, recent innovative and promising approaches to engineering SG models are described. Finally, this review discusses the different challenges and future perspectives in SG bioengineering.
Circulating levels of AGEs and soluble RAGE isoforms are associated with all-cause mortality and development of cardiovascular complications in type 2 diabetes: a retrospective cohort study
Authors: Sabbatinelli Jacopo , Castiglione Stefania , Macrì Federica , Giuliani Angelica , Ramini Deborah , Vinci Maria Cristina , Tortato Elena , Bonfigli Anna Rita , Olivieri Fabiola , Raucci Angela 
Published: June 2022

Abstract
Background
Advanced glycation end-products (AGEs) and their interaction with the receptor for advanced glycation end-products (RAGE) play a pivotal role in the development and progression of type 2 diabetes. In this retrospective cohort study, we explored the association of circulating levels of soluble RAGE (sRAGE) isoforms, i.e., endogenous secretory esRAGE and cleaved cRAGE, AGEs and their respective ratios with 15-year all-cause mortality in type 2 diabetes.

Methods
Baseline AGEs and sRAGE isoforms concentration were measured by ELISA in 362 patients with type 2 diabetes and in 125 age- and gender-matched healthy control subjects (CTR). Independent predictors of mortality were determined using Cox proportional-hazards models and used to build and validate a nomogram for all-cause mortality prediction in type 2 diabetes.

Results
AGEs, total sRAGE, cRAGE and the AGEs/sRAGE and AGEs/esRAGE ratios were significantly increased in patients with type 2 diabetes compared to CTR (p < 0.001). In CTR subjects, but not in type 2 diabetes patients, a significant negative correlation between cRAGE and age was confirmed (p = 0.003), whereas the AGEs/sRAGE (p = 0.032) and AGEs/cRAGE (p = 0.006) ratios were positively associated with age. At an average follow-up of 15 years (4,982 person-years), 130 deaths were observed. The increase in the AGEs/cRAGE ratio was accompanied by a higher risk of all-cause mortality in patients with type 2 diabetes (HR per each SD increment = 1.30, 95% CI 1.15–1.47; p < 0.001). Moreover, sRAGE was associated with the development of major adverse cardiovascular events (MACE) in type 2 diabetes patients without previous MACE (OR for each SD increase: 1.48, 95% CI 1.11–1.89). A nomogram based on age, sex, HbA1c, systolic blood pressure, and the AGEs/cRAGE ratio was built to predict 5-, 10- and 15-year survival in type 2 diabetes. Patients were categorized into quartiles of the monogram scores and Kaplan-Meier survival curves confirmed the prognostic accuracy of the model (log-rank p = 6.5 × 10− 13).

Conclusions
The ratio between AGEs and the cRAGE isoform is predictive of 15-year survival in patients with type 2 diabetes. Our data support the assessment of circulating AGEs and soluble RAGE isoforms in patients with type 2 diabetes as predictors of MACE and all-cause mortality.
CircVAPA promotes small cell lung cancer progression by modulating the miR-377-3p and miR-494-3p/IGF1R/AKT axis
Authors: Hua Jinghan , Wang Xiaolin , Ma Liying , Li Jingxin , Cao Guozhen , Zhang Shaobo , Lin Wenchu 
Published: June 2022

Abstract
Background
Multiple lines of evidence have demonstrated that circular RNAs (circRNAs) play oncogenic or tumor-suppressive roles in various human cancers. Nevertheless, the biological functions of circRNAs in small cell lung cancer (SCLC) are still elusive.

Methods
CircVAPA (annotated as hsa_circ_0006990) was identified by mining the circRNA profiling dataset of six paired SCLC tissues and the RNA-seq data of serum samples from 36 SCLC patients and 118 healthy controls. The circVAPA expression level was evaluated using quantitative real-time PCR in SCLC cells and tissues. Cell viability, colony formation, cell cycle and apoptosis analysis assays and in vivo tumorigenesis were used to reveal the biological roles of circVAPA. The underlying mechanism of circVAPA was investigated by Western blot, RNA pulldown, RNA immunoprecipitation, dual-luciferase reporter assay and rescue experiments.

Results
We revealed that circVAPA, derived from exons 2-4 of the vesicle-associated membrane protein-associated protein A (VAPA) gene, exhibited higher expression levels in SCLC cell lines, clinical tissues, and serum from SCLC patients than the controls, and facilitated SCLC progression in vitro and in vivo. Mechanistically, circVAPA activated the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway by modulating the miR-377-3p and miR-494-3p/insulin-like growth factor 1 receptor (IGF1R) axis to accelerate SCLC progression. Furthermore, circVAPA depletion markedly enhanced the inhibitory effects of BMS-536924, an IGF1R kinase inhibitor in cellular and xenograft mouse models.

Conclusions
CircVAPA promotes SCLC progression via the miR-377-3p and miR-494-3p/IGF1R/AKT axis. We hope to develop clinical protocols of combinations of circVAPA inhibition and BMS-536924 addition for treating SCLC with circVAPA upregulation.
Identifying the critical states and dynamic network biomarkers of cancers based on network entropy
Authors: Liu Juntan , Ding Dandan , Zhong Jiayuan , Liu Rui 
Published: June 2022

AbstractBackgroundThere are sudden deterioration phenomena during the progression of many complex diseases, including most cancers; that is, the biological system may go through a critical transition from one stable state (the normal state) to another (the disease state). It is of great importance to predict this critical transition or the so-called pre-disease state so that patients can receive appropriate and timely medical care. In practice, however, this critical transition is usually difficult to identify due to the high nonlinearity and complexity of biological systems.MethodsIn this study, we employed a model-free computational method, local network entropy (LNE), to identify the critical transition/pre-disease states of complex diseases. From a network perspective, this method effectively explores the key associations among biomolecules and captures their dynamic abnormalities.ResultsBased on LNE, the pre-disease states of ten cancers were successfully detected. Two types of new prognostic biomarkers, optimistic LNE (O-LNE) and pessimistic LNE (P-LNE) biomarkers, were identified, enabling identification of the pre-disease state and evaluation of prognosis. In addition, LNE helps to find “dark genes” with nondifferential gene expression but differential LNE values.ConclusionsThe proposed method effectively identified the critical transition states of complex diseases at the single-sample level. Our study not only identified the critical transition states of ten cancers but also provides two types of new prognostic biomarkers, O-LNE and P-LNE biomarkers, for further practical application. The method in this study therefore has great potential in personalized disease diagnosis.
Health system resilience during COVID-19 understanding SRH service adaptation in North Kivu
Authors: Ho Lara S. , Bertone Maria Paola , Mansour Wesam , Masaka Cyprien , Kakesa Jessica 
Published: June 2022

Abstract
Background
There is often collateral damage to health systems during epidemics, affecting women and girls the most, with reduced access to non-outbreak related services, particularly in humanitarian settings. This rapid case study examines sexual and reproductive health (SRH) services in the Democratic Republic of the Congo when the COVID-19 hit, towards the end of an Ebola Virus Disease (EVD) outbreak, and in a context of protracted insecurity.

Methods
This study draws on quantitative analysis of routine data from four health zones, a document review of policies and protocols, and 13 key-informant interviews with staff from the Ministry of Public Health, United Nations agencies, international and national non-governmental organizations, and civil society organizations.

Results
Utilization of SRH services decreased initially but recovered by August 2020. Significant fluctuations remained across areas, due to the end of free care once Ebola funding ceased, insecurity, number of COVID-19 cases, and funding levels. The response to COVID-19 was top-down, focused on infection and prevention control measures, with a lack of funding, technical expertise and overall momentum that characterized the EVD response. Communities and civil society did not play an active role for the planning of the COVID-19 response. While health zone and facility staff showed resilience, developing adaptations to maintain SRH provision, these adaptations were short-lived and inconsistent without external support and funding.

Conclusion
The EVD outbreak was an opportunity for health system strengthening that was not sustained during COVID-19. This had consequences for access to SRH services, with limited-resources available and deprioritization of SRH.
Two metrics on rooted unordered trees with labels
Authors: Wang Yue 
Published: June 2022

Abstract
Background
The early development of a zygote can be mathematically described by a developmental tree. To compare developmental trees of different species, we need to define distances on trees. If children cells after a division are not distinguishable, developmental trees are represented by the space $${\mathcal {T}}$$
T
of rooted trees with possibly repeated labels, where all vertices are unordered. If children cells after a division are partially distinguishable, developmental trees are represented by the space $${\mathcal {P}}$$
P
of rooted trees with possibly repeated labels, where vertices can be ordered or unordered.

Results
On $${\mathcal {T}}$$
T
, the space of rooted unordered trees with possibly repeated labels, we define two metrics: the best-match metric and the left-regular metric, which show some advantages over existing methods. On $${\mathcal {P}}$$
P
, the space of rooted labeled trees with ordered or unordered vertices, there is no metric, and we define a semimetric, which is a variant of the best-match metric. To compute the best-match distance between two trees, the expected time complexity and worst-case time complexity are both $${\mathcal {O}}(n^2)$$

O
(

n
2

)

, where n is the tree size. To compute the left-regular distance between two trees, the expected time complexity is $${\mathcal {O}}(n)$$

O
(
n
)

, and the worst-case time complexity is $${\mathcal {O}}(n\log n)$$

O
(
n
log
n
)

.

Conclusions
For rooted labeled trees with (fully/partially) unordered vertices, we define metrics (semimetric) that have fast algorithms to compute and have advantages over existing methods. Such trees also appear outside of developmental biology, and such metrics can be applied to other types of trees which have more extensive applications, especially in molecular biology.
Ruxolitinib-corticosteroid as first-line therapy for newly diagnosed high-risk acute graft versus host disease: study protocol for a multicenter, randomized, phase II controlled trial
Authors: Dou Liping , Peng Bo , Li Xin , Wang Lu , Jia Mingyu , Xu Lingmin , Li Fei , Liu Daihong 
Published: June 2022

Abstract
Background
The response rate of the first-line therapy with corticosteroid for acute graft versus host disease (aGVHD) is about 50%, and steroid-refractory disease is associated with high mortality. The improved response rate to the first-line therapy of newly diagnosed aGVHD patients would result in therapeutic benefits. Ruxolitinib, a selective Janus kinase (JAK) 1/2 inhibitor, has been approved for the treatment of steroid-refractory acute GVHD. The addition of ruxolitinib to the first-line therapy may improve the efficacy of corticosteroids.

Methods
This investigator-initiated, open-label, multicenter, prospective randomized, and controlled two-arm phase II study compares the efficacy and safety of ruxolitinib combined with 1 mg/kg methylprednisolone versus 2 mg/kg methylprednisolone alone in newly diagnosed aGVHD patients. Patients with intermediate or high-risk aGVHD, as defined by the Minnesota aGVHD high-risk score and biomarker algorithm, are eligible for this study. A total of 198 patients will be randomized at a 1:1 ratio and assigned a GVHD risk (intermediate versus high risk) and disease status before transplantation (complete remission versus no complete remission). The primary endpoint is the overall response rate on day 28, which is defined as an improvement of at least one stage in the severity of aGVHD in one organ without deterioration in any other organ or disappearance of any GVHD signs from all organs without requiring new systemic immunosuppressive treatment. The secondary objectives consist of response time, response duration, overall survival, disease-free survival, non-relapse mortality, failure-free survival, and changes in serum levels of proinflammatory cytokines and GVHD-related biomarkers.

Discussion
This open-label, multicenter, two-arm randomized trial will evaluate whether the addition of ruxolitinib combined with corticosteroid is superior to corticosteroid alone in newly diagnosed high-risk aGVHD.

Trial registration
ClinicalTrials.gov NCT04061876 (version number: 2019.5.18). Registered on July 16, 2019