bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiation oncologists’ attitudes and beliefs about intensity-modulated radiation therapy and stereotactic body radiation therapy for prostate cancer
Authors: Jacobs Bruce L. , Hamm Megan , de Abril Cameron Flor , Luiggi-Hernandez Jose G. , Heron Dwight E. , Kahn Jeremy M. , Barnato Amber E. 
Published: August 2020

Abstract
Background
To better understand how radiation oncologists perceive intensity-modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) for prostate cancer and how these perceptions may influence treatment decisions.

Methods
We conducted semi-structured interviews of radiation oncologists between January–May, 2016. We used a purposeful sampling technique to select participants across a wide range of experience, regions, and practice types. Two trained qualitative researchers used an inductive, iterative approach to code transcripts and identify themes. We then used content analysis and thematic analysis of the coded transcripts to understand radiation oncologists’ attitudes and beliefs about IMRT and SBRT.

Results
Thematic saturation was achieved after 20 interviews. Participants were affiliated with academic (n = 13; 65%), private (n = 5; 25%), and mixed (n = 2; 10%) practices and had a wide range of clinical experience (median 19 years; range 4–49 years). Analysis of interview transcripts revealed four general themes: 1) most radiation oncologists offered surgery, brachytherapy, IMRT, and active surveillance for low-risk patients; 2) there was no consensus on the comparative effectiveness of IMRT and SBRT; 3) key barriers to adopting SBRT included issues related to insurance, reimbursement, and practice inertia; and 4) despite these barriers, most participants envisioned SBRT use increasing over the next 5–10 years.

Conclusions
In the absence of strong opinions about effectiveness, nonclinical factors influence the choice of radiation treatment. Despite a lack of consensus, most participants agreed SBRT may become a standard of care in the future.
The role of transformational leadership, job demands and job resources for patient safety culture in Norwegian nursing homes: a cross-sectional study
Authors: Seljemo Camilla , Viksveen Petter , Ree Eline 
Published: August 2020

Abstract
Background
Transformational leadership style is considered to be of importance to increase patient safety, to facilitate a balance between job resources and job demands, and to create a sound patient safety culture within health care services. However, there is limited research assessing these associations within the context of nursing homes. The aim of this study was to assess the association between transformational leadership, job demands and job resources; and patient safety culture and employees’ overall perception of patient safety in nursing homes.

Method
A cross-sectional survey of employees in four Norwegian nursing homes was conducted (N = 165). Multiple hierarchical regression analysis was used to assess the explained variance of transformational leadership, job demands and job resources on patient safety culture and overall perception of patient safety.

Results
Transformational leadership explained 47.2% of the variance in patient safety culture and 25.4% of overall perception of patient safety, controlling for age and gender (p < 0.001). Additionally, job demands and job resources explained 7.8% of patient safety culture and 4.7% of overall perception of patient safety (p < 0.001).

Conclusion
Implementing transformational leadership style may be important in creating and sustaining sound patient safety culture in nursing homes. Furthermore, leaders should make an effort to facilitate a good work environment with an optimal balance between job demands and job resources, as this in turn might have a positive influence on patient safety culture.
Motivations, experiences and aspirations of trainee nursing associates in England: a qualitative study
Authors: King Rachel , Ryan Tony , Wood Emily , Tod Angela , Robertson Steve 
Published: August 2020

Abstract
Background
The nursing associate role was developed in England in response to the ‘Shape of Caring’ review. It has been implemented to fulfil two aims; to bridge the gap between registered nurses and healthcare assistants, and to provide an alternative route into registered nursing in light of workforce shortages.
Other high income countries deploy second level nurses within their healthcare systems, however the UK has a turbulent history with such roles. The previous state enrolled nurse was phased out in the 1990s, and more recently the assistant practitioner (AP) role has faced wide variation in titles, scope and pay. Little is known about those who have embarked on the new nursing associate training course and their experiences of the role.

Methods
An exploratory qualitative study was undertaken using focus groups of trainee nursing associates to generate in-depth discussion about their motivations, experiences of training, and career aspirations.
Three focus groups (n = 15) took place in December 2018 using a purposive sample of trainee nursing associates registered at a University in the North of England. Two researchers facilitated each group discussion at a time and place convenient for participants. The discussions were audio recorded, transcribed and data was analysed thematically.

Results
This study found that trainee nursing associates are motivated by affordable, local, career development. During training they face challenges relating to clinical support, academic workload and uncertainty about future career opportunities. They experience role ambiguity both individually and across the wider organisation. Trainee nursing associates rely on broad support networks to build their occupational identity.

Conclusions
The barriers and facilitators of trainee nursing associate personal development have implications for policy and practice relating to recruitment and retention. The results increase our understanding of this emerging role, and have informed the development of a larger longitudinal cohort study. Further research is required to evaluate the impact of this new role.
Planning the scale up of brief psychological interventions using theory of change
Authors: Fuhr Daniela C. , Acarturk Ceren , Sijbrandij Marit , Brown Felicity L. , Jordans Mark J. D. , Woodward Aniek , McGrath Michael , Sondorp Egbert , Ventevogel Peter , Ikkursun Zeynep , El Chammay Rabih , Cuijpers Pim , Roberts Bayard 
Published: August 2020

Abstract
Background
A large mental health treatment gap exists among conflict-affected populations, and Syrian refugees specifically. Promising brief psychological interventions for conflict-affected populations exist such as the World Health Organization’s Problem Management Plus (PM+) and the Early Adolescent Skills for Emotions (EASE) intervention, however, there is limited practical guidance for countries of how these interventions can be taken to scale. The aim of this study was to unpack pathways for scaling up PM+ and EASE for Syrian refugees.

Methods
We conducted three separate Theory of Change (ToC) workshops in Turkey, the Netherlands, and Lebanon in which PM+ and EASE are implemented for Syrian refugees. ToC is a participatory planning process involving key stakeholders, and aims to understand a process of change by mapping out intermediate and long-term outcomes on a causal pathway. 15–24 stakeholders were invited per country, and they participated in a one-day interactive ToC workshop on scaling up.

Results
A cross-country ToC map for scale up brief psychological interventions was developed which was based on three country-specific ToC maps. Two distinct causal pathways for scale up were identified (a policy and financing pathway, and a health services pathway) which are interdependent on each other. A list of key assumptions and interventions which may hamper or facilitate the scaling up process were established.

Conclusion
ToC is a useful tool to help unpack the complexity of scaling up. Our approach highlights that scaling up brief psychological interventions for refugees builds on structural changes and reforms in policy and in health systems. Both horizontal and vertical scale up approaches are required to achieve sustainability. This paper provides the first theory-driven map of causal pathways to help support the scaling-up of evidence-based brief psychological interventions for refugees and populations in global mental health more broadly.
Genome-wide association meta-analysis for early age-related macular degeneration highlights novel loci and insights for advanced disease
Authors: Winkler Thomas W. , Grassmann Felix , Brandl Caroline , Kiel Christina , Günther Felix , Strunz Tobias , Weidner Lorraine , Zimmermann Martina E. , Korb Christina A. , Poplawski Alicia , Schuster Alexander K. , Müller-Nurasyid Martina , Peters Annette , Rauscher Franziska G. , Elze Tobias , Horn Katrin , Scholz Markus , Cañadas-Garre Marisa , McKnight Amy Jayne , Quinn Nicola , Hogg Ruth E. , Küchenhoff Helmut , Heid Iris M. , Stark Klaus J. , Weber Bernhard H. F. 
Published: August 2020

Abstract
Background
Advanced age-related macular degeneration (AMD) is a leading cause of blindness. While around half of the genetic contribution to advanced AMD has been uncovered, little is known about the genetic architecture of early AMD.

Methods
To identify genetic factors for early AMD, we conducted a genome-wide association study (GWAS) meta-analysis (14,034 cases, 91,214 controls, 11 sources of data including the International AMD Genomics Consortium, IAMDGC, and UK Biobank, UKBB). We ascertained early AMD via color fundus photographs by manual grading for 10 sources and via an automated machine learning approach for > 170,000 photographs from UKBB. We searched for early AMD loci via GWAS and via a candidate approach based on 14 previously suggested early AMD variants.

Results
Altogether, we identified 10 independent loci with statistical significance for early AMD: (i) 8 from our GWAS with genome-wide significance (P < 5 × 10− 8), (ii) one previously suggested locus with experiment-wise significance (P < 0.05/14) in our non-overlapping data and with genome-wide significance when combining the reported and our non-overlapping data (together 17,539 cases, 105,395 controls), and (iii) one further previously suggested locus with experiment-wise significance in our non-overlapping data. Of these 10 identified loci, 8 were novel and 2 known for early AMD. Most of the 10 loci overlapped with known advanced AMD loci (near ARMS2/HTRA1, CFH, C2, C3, CETP, TNFRSF10A, VEGFA, APOE), except two that have not yet been identified with statistical significance for any AMD. Among the 17 genes within these two loci, in-silico functional annotation suggested CD46 and TYR as the most likely responsible genes. Presence or absence of an early AMD effect distinguished the known pathways of advanced AMD genetics (complement/lipid pathways versus extracellular matrix metabolism).

Conclusions
Our GWAS on early AMD identified novel loci, highlighted shared and distinct genetics between early and advanced AMD and provides insights into AMD etiology. Our data provide a resource comparable in size to the existing IAMDGC data on advanced AMD genetics enabling a joint view. The biological relevance of this joint view is underscored by the ability of early AMD effects to differentiate the major pathways for advanced AMD.
Association of blood pressure with cognitive function at midlife: a Mendelian randomization study
Authors: Sun Daokun , Thomas Emy A. , Launer Lenore J. , Sidney Stephen , Yaffe Kristine , Fornage Myriam 
Published: August 2020

Abstract
Background
Whether high blood pressure has a causal effect on cognitive function as early as middle age is unclear. We investigated whether high blood pressure (BP) causally impairs cognitive function at midlife using Mendelian Randomization (MR).

Methods
We applied a two-sample MR approach to investigate the causal relationship between BP and midlife cognitive performance measured by the Digit Symbol Substitution Test (DSST), Rey Auditory Verbal Learning Test (RAVLT), and Stroop Interference test. We used a total of 109 genetic polymorphisms with established associations with BP as instrumental variables and estimated gene-cognitive function association in 1369 middle-aged adults (Mean age (SD): 50.8 (3.3), 54.0% women) from the CARDIA study.

Results
A 10 mmHg increment in genetically-predicted systolic, diastolic, or pulse pressure was associated with a 4.9 to 7.7-point lower DSST score (P = 0.002, SBP; P = 0.005, DBP and P = 0.008, PP), while a 10 mmHg increment in genetically-predicted SBP was associated with a 0.7 point lower RAVLT and a 2.3 point higher Stroop (P = 0.046 and 0.011, respectively).

Conclusions
This MR analysis shows that high BP, especially SBP, is causally associated with poorer processing speed, verbal memory, and executive function during midlife. These findings emphasize the need for further investigation of the role and mechanisms of BP dysregulation on cognitive health in middle age and perhaps, more broadly, across the lifespan.
CXCR4+ cells are increased in lung tissue of patients with idiopathic pulmonary fibrosis
Authors: Jaffar Jade , Griffiths Kate , Oveissi Sara , Duan Mubing , Foley Michael , Glaspole Ian , Symons Karen , Organ Louise , Westall Glen 
Published: August 2020

Abstract
Background
CXCR4, a transmembrane-receptor located on epithelial cells that is activated by CXCL12, may have a role in IPF via migration of CXCR4+ fibrocytes to the lung. However, its expression has not been fully characterised in idiopathic pulmonary fibrosis (IPF) or other fibrotic interstitial lung diseases (ILDs). CXCL12 is constitutively expressed in the bone marrow, and levels of CXCR4 regulate control of this signalling pathway. The aim of this study was to profile the expression of CXCR4 in lung tissue and peripheral circulation of patients with IPF and other fibrotic ILDs.

Methods
Expression of CXCR4 on peripheral blood mononuclear cells (PBMCs) was examined by flow cytometry in 20 patients with IPF and 10 age-matched non-disease control (NDC) donors. Levels of CXCL12 in human plasma were measured by ELISA. Expression of CXCR4, CXCL12, CD45, and e-cadherin was assessed in IPF (n = 10), other fibrotic ILD (n = 8) and NDC (n = 10) lung tissue by multiplex immunohistochemistry (OPAL) and slides were scanned using a Vectra 3 scanner. Cells were quantified with computer automated histological analysis software (HALO).

Results
In blood, the number of CXCR4+ cells was lower but the level of CXCL12 was higher in patients with IPF compared to NDC donors. Elevated CXCR4 expression was detected in lung tissue from patients with IPF and other fibrotic ILDs compared to NDC. There were higher levels of CXCR4+/e-cadherin+/CXCL12+ (epithelial) cells in IPF lung tissue compared to NDC, but there was no difference in the numbers of CXCR4+/CD45+/CXCL12+ (myeloid) cells between the two groups.

Conclusions
This report demonstrates that CXCR4 is overexpressed not only in IPF but also in other ILDs and expression is particularly prominent within both honeycomb cysts and distal airway epithelium. This observation supports the hypothesis that CXCR4 may drive tissue fibrosis through binding its specific ligand CXCL12. Although CXCR4 expressing cells could be either of epithelial or myeloid origin it appears that the former is more prominent in IPF lung tissue. Further characterization of the cells of the honeycomb cyst may lead to a better understanding of the fibrogenic processes in IPF and other end-stage fibrotic ILDs.
CircRNA hsa_circRNA_0001776 inhibits proliferation and promotes apoptosis in endometrial cancer via downregulating LRIG2 by sponging miR-182
Authors: Jia Youjuan , Liu Meijuan , Wang Shuxia 
Published: August 2020

Abstract
Background
Endometrial cancer (EC) is a common malignancy of the female reproductive system. Circular RNAs (circRNAs) were demonstrated to exert critical roles in cancers, including EC. This study aimed to investigate the effects of hsa_circRNA_0001776 (circ_0001776) on EC.

Methods
Real-time quantitative PCR (RT-qPCR) was used to measure circ_0001776, microRNA-182 (miR-182) and leucine-rich repeats and immunoglobulin-like domains 2 (LRIG2) expression. The diagnostic and prognostic values of circ_0001776 were identified by receiver operating characteristic (ROC) curve analysis and survival analysis, respectively. RNase R digestion was used to characterize circ_0001776, and the localization of circ_0001776 was evaluated by cell fractionation assay. Then, cell counting kit-8 (CCK-8), colony formation, and flow cytometry analysis were used to detect cell proliferation and apoptosis, respectively. The real-time glycolytic rate (ECAR) and lactate production were measured by extracellular flux analysis and a lactate assay kit, respectively. Bioinformatics analysis and dual-luciferase reporter assay were used to determine the interaction among circ_0001776, miR-182 and LRIG2. The protein expression of LRIG2 was determined by western blot. Moreover, circ_0001776 overexpression vector was used to upregulate circ_0001776 expression in an animal tumor model.

Results
Circ_0001776 and LRIG2 were downregulated, while miR-182 was upregulated in EC tissues and cells. Low expression of circ_0001776 was correlated with the 5-year survival rate of EC patients. Upregulated circ_0001776 markedly attenuated cell proliferation and glycolysis, and enhanced cell apoptosis. Besides, circ_0001776 sponged miR-182 to regulate LRIG2 expression. Circ_0001776 could suppress EC progression by miR-182/LRIG2 axis. Furthermore, we also found that circ_0001776 significantly inhibited tumor growth in vivo.

Conclusion
Our results confirmed that circ_0001776 inhibited EC tumorigenesis and progression via miR-182/LRIG2 axis, providing a potential therapeutic target for EC.
Cryptotanshinone chemosensitivity potentiation by TW-37 in human oral cancer cell lines by targeting STAT3–Mcl-1 signaling
Authors: Yang In-Hyoung , Hong Seung-Hyun , Jung Minjung , Ahn Chi-Hyun , Yoon Hye-Jung , Hong Seong Doo , Cho Sung-Dae , Shin Ji-Ae 
Published: August 2020

Abstract
Background
Despite being one of the leading cancer types in the world, the diagnosis of oral cancer and its suitable therapeutic options remain limited. This study aims to investigate the single and chemosensitizing effects of TW-37, a BH3 mimetic in oral cancer, on human oral cancer cell lines.

Methods
We assessed the single and chemosensitizing effects of TW-37 in vitro using trypan blue exclusion assay, Western blotting, DAPI staining, Annexin V–FITC/PI double staining, and quantitative real-time PCR. Mcl-1 overexpression models were established by transforming vector and transient transfection was performed to test for apoptosis

Results
TW-37 enhanced the cytotoxicity of human oral cancer cell lines by inducing caspase-dependent apoptosis, which correlates with the reduction of the myeloid cell leukemia-1 (Mcl-1) expression via transcriptional and post-translational regulation. The ectopic expression of Mcl-1 partially attenuated the apoptosis-inducing capacity of TW-37 in human oral cancer cell lines. Besides, TW-37 decreased the phosphorylation of signal transducer and activator of transcription 3 (STAT3) at Tyr705 and nuclear translocation in human oral cancer cell lines at the early time points. Furthermore, TW-37 potentiated chemosusceptibility of cryptotanshinone in human oral cancer cell lines by suppressing STAT3–Mcl-1 signaling compared with either TW-37 or cryptotanshinone alone, resulting in potent apoptosis.

Conclusions
This study not only unravels the single and chemosensitizing effects of TW-37 for treatment of human oral cancer but also highlights the likelihood of TW-37 as a good therapeutic strategy to enhance the prognosis of patients with oral cancer in the future.
High CENPM mRNA expression and its prognostic significance in hepatocellular carcinoma: a study based on data mining
Authors: Wu Zeng-hong , Yang Dong-liang 
Published: August 2020

Abstract
Background
Hepatocellular carcinoma (HCC) is a high mortality disease, the fifth most general cancer worldwide, and the second leading to cancer-related deaths, with more than 500,000 new patients diagnosed each year. First, the high expression of centromere M (CENPM) in mammary gland tissue of b-catenin transformed mice was identified.

Materials and methods
In our study, we evaluated the expression of CENPM in hepatocellular carcinoma based on data obtained from an online database. Multivariate analysis showed that the expression of CENPM and M classification was an independent prognostic factor for patients with hepatocellular carcinoma.

Results
Survival analysis showed that patients with high CENPM had a worse prognosis than patients with low CENPM (P < 0.01). A multivariate Cox regression hazard model showed that B cells, CD8+ T cells, macrophages, and dendritic cells infiltrated by immune cells were statistically significant in liver cancer (P < 0.05). Using the network, the 50 most frequently changed neighbor genes of CENPM were shown, and the most common change was RAD21 (18.3%).

Conclusion
Our study found that the expression of CENPM was significantly increased in patients with hepatocellular carcinoma, and it was related to a variety of clinical characteristics, its correlation with the level of immune infiltration and poor prognosis, so CENPM can be used as a useful prognosis for patients’ markers and HCC.
Molecular surveillance reveals the presence of pfhrp2 and pfhrp3 gene deletions in Plasmodium falciparum parasite populations in Uganda, 2017–2019
Authors: Agaba Bosco B. , Anderson Karen , Gresty Karryn , Prosser Christiane , Smith David , Nankabirwa Joaniter I. , Nsobya Sam , Yeka Adoke , Opigo Jimmy , Gonahasa Samuel , Namubiru Rhoda , Arinaitwe Emmanuel , Mbaka Paul , Kissa John , Won Sungho , Lee Bora , Lim Chae Seung , Karamagi Charles , Cunningham Jane , Nakayaga Joan K. , Kamya Moses R. , Cheng Qin 
Published: August 2020

Abstract
Background
Histidine-rich protein-2 (HRP2)-based rapid diagnostic tests (RDTs) are the only RDTs recommended for malaria diagnosis in Uganda. However, the emergence of Plasmodium falciparum histidine rich protein 2 and 3 (pfhrp2 and pfhrp3) gene deletions threatens their usefulness as malaria diagnostic and surveillance tools. The pfhrp2 and pfhrp3 gene deletions surveillance was conducted in P. falciparum parasite populations in Uganda.

Methods
Three-hundred (n = 300) P. falciparum isolates collected from cross-sectional malaria surveys in symptomatic individuals in 48 districts of eastern and western Uganda were analysed for the presence of pfhrp2 and pfhrp3 genes. Presence of parasite DNA was confirmed by PCR amplification of the 18s rRNA gene, msp1 and msp2 single copy genes. Presence or absence of deletions was confirmed by amplification of exon1 and exon2 of pfhrp2 and pfhrp3 using gene specific PCR.

Results
Overall, pfhrp2 and pfhrp3 gene deletions were detected in 29/300 (9.7%, 95% CI 6.6–13.6%) parasite isolates. The pfhrp2 gene was deleted in 10/300 (3.3%, 95% CI 1.6–6.0%) isolates, pfhrp3 in 9/300 (3.0%, 95% CI 1.4–5.6%) while both pfhrp2 and pfhrp3 were deleted in 10/300 (3.3%, 95% CI 1.6–6.0%) parasite isolates. Proportion of pfhrp2/3 deletions was higher in the eastern 14.7% (95% CI 9.7–20.0%) compared to the western region 3.1% (95% CI 0.8–7.7%), p = 0.001. Geographical location was associated with gene deletions aOR 6.25 (2.02–23.55), p = 0.003.

Conclusions
This is the first large-scale survey reporting the presence of pfhrp2/3 gene deletions in P. falciparum isolates in Uganda. Roll out of RDTs for malaria diagnosis should take into consideration the existence of pfhrp2/3 gene deletions particularly in areas where they were detected. Periodic pfhrp2/3 surveys are recommended to inform future decisions for deployment of alternative RDTs.