bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neonatal nursing led research activity in the UK: a survey of current practice
Authors: Gallagher Katie , Petty Julia , Cooper Joanne , Marlow Neil 
Published: October 2021

Abstract
Background
Neonatal nurses are ideally placed in practice to undertake research enhancing the care of families. More information is required, however, around neonatal nursing led research to advance leadership in this area. The aim of this study was to determine neonatal nursing led research activity within the UK.

Methods
The study used a web-based survey design and neonatal nurses were eligible if they were working at or towards Masters or Doctoral level qualification in the UK. The survey was distributed to members of the Neonatal Nurses Association, UK Schools of Nursing and shared on social media pages of authors and professional organisations. Results were analysed using descriptive and frequency statistics and content analysis.

Results
Of the 56 respondents, 14% (n = 8) had a Doctoral level qualification and 43% (n = 24) of participants held a Masters qualification. Lack of time and funding knowledge was the largest barrier to research. Only 30% (n = 3) of participants had a research mentor and only 18% (n = 3) were from a neonatal nursing background.

Conclusions
There are limited numbers of neonatal nurses undertaking or leading nursing research in the UK. Further support is required to enhance clinical academic career trajectories to ensure research is a viable pathway for future generations of neonatal nurses.
The cost-saving effect of continuity of care (COC): an analysis of institutional COC on diabetic treatment costs using panel 2SLS regressions
Authors: Wen Yu-Ping , Liu Sandra S. , Sheu Ji-Tian , Wang Hong-Huei , Becker Edmund R. , Lu Jui-fen Rachel 
Published: October 2021

Abstract
Background
The high costs of chronic conditions call for new treatment approaches that reduce costs while ensuring desirable health outcomes. There has been a growing transformation of care delivery models from conventional referral systems to integrated care models. This study seeks to evaluate the cost-saving impact of integrated care delivery model under pay-for-performance (P4P) scheme with continuity of care at institution level (ICOC).

Methods
We analyzed the Taiwan National Health Insurance claim data of 21,725 diabetic patients who visited clinics and/or hospitals at least four times a year for 8 years. Using average local provider P4P participation rate (for each accreditation level) as an instrumental variable in two-stage least squares (2SLS) regressions, we have estimated consistent estimates of the ICOC elasticities for all-cause inpatient and outpatient costs.

Results
Our results show that ICOC significantly reduced inpatient costs but increased outpatient costs with the elasticity for treatment costs of -11.6 and 1.03, respectively. The decrease in inpatient costs offset the increase in outpatient costs and the resulting total cost saving showed significant association with ICOC. The saving effect of ICOC is especially robust among patients who used clinics as their principal source of care.

Conclusions
Institutional continuity of care has a substantial impact on the treatment costs of diabetes patients. In the context where inpatient care costs are significantly higher than that of the outpatient care, ICOC would lead to a meaningful cost-saving effect. For new diabetes patients, care by clinics demonstrated the strongest saving effect.
SaferBirths bundle of care protocol: a stepped-wedge cluster implementation project in 30 public health-facilities in five regions, Tanzania
Authors: Kamala Benjamin A. , Ersdal Hege L. , Mduma Estomih , Moshiro Robert , Girnary Sakina , Østrem Ole Terje , Linde Jørgen , Dalen Ingvild , Søyland Elsa , Bishanga Dunstan R. , Bundala Felix Ambrose , Makuwani Ahmad M. , Richard Boniphace Marwa , Muzzazzi Pius David , Kamala Ivony , Mdoe Paschal F. 
Published: October 2021

Abstract
Background
The burden of stillbirth, neonatal and maternal deaths are unacceptably high in low- and middle-income countries, especially around the time of birth. There are scarce resources and/or support implementation of evidence-based training programs. SaferBirths Bundle of Care is a well-proven package of innovative tools coupled with data-driven on-the-job training aimed at reducing perinatal and maternal deaths. The aim of this project is to determine the effect of scaling up the bundle on improving quality of intrapartum care and perinatal survival.

Methods
The project will follow a stepped-wedge cluster implementation design with well-established infrastructures for data collection, management, and analysis in 30 public health facilities in regions in Tanzania. Healthcare workers from selected health facilities will be trained in basic neonatal resuscitation, essential newborn care and essential maternal care. Foetal heart rate monitors (Moyo), neonatal heart rate monitors (NeoBeat) and skills trainers (NeoNatalie Live) will be introduced in the health facilities to facilitate timely identification of foetal distress during labour and improve neonatal resuscitation, respectively. Heart rate signal-data will be automatically collected by Moyo and NeoBeat, and newborn resuscitation training by NeoNatalie Live.
Given an average of 4000 baby-mother pairs per year per health facility giving an estimate of 240,000 baby-mother pairs for a 2-years duration, 25% reduction in perinatal mortality at a two-sided significance level of 5%, intracluster correlation coefficient (ICC) to be 0.0013, the study power stands at 0.99.

Discussion
Previous reports from small-scale Safer Births Bundle implementation studies show satisfactory uptake of interventions with significant improvements in quality of care and lives saved. Better equipped and trained birth attendants are more confident and skilled in providing care. Additionally, local data-driven feedback has shown to drive continuous quality of care improvement initiatives, which is essential to increase perinatal and maternal survival. Strengths of this research project include integration of innovative tools with existing national guidelines, local data-driven decision-making and training. Limitations include the stepwise cluster implementation design that may lead to contamination of the intervention, and/or inability to address the shortage of healthcare workers and medical supplies beyond the project scope.

Trial registration
Name of Trial Registry: ISRCTN Registry.
Trial registration number: ISRCTN30541755.
Date of Registration: 12/10/2020.
Type of registration: Prospectively Registered.
Non-destructive quantification of anaerobic gut fungi and methanogens in co-culture reveals increased fungal growth rate and changes in metabolic flux relative to mono-culture
Authors: Leggieri Patrick A. , Kerdman-Andrade Corey , Lankiewicz Thomas S. , Valentine Megan T. , O’Malley Michelle A. 
Published: October 2021

AbstractBackgroundQuantification of individual species in microbial co-cultures and consortia is critical to understanding and designing communities with prescribed functions. However, it is difficult to physically separate species or measure species-specific attributes in most multi-species systems. Anaerobic gut fungi (AGF) (Neocallimastigomycetes) are native to the rumen of large herbivores, where they exist as minority members among a wealth of prokaryotes. AGF have significant biotechnological potential owing to their diverse repertoire of potent lignocellulose-degrading carbohydrate-active enzymes (CAZymes), which indirectly bolsters activity of other rumen microbes through metabolic exchange. While decades of literature suggest that polysaccharide degradation and AGF growth are accelerated in co-culture with prokaryotes, particularly methanogens, methods have not been available to measure concentrations of individual species in co-culture. New methods to disentangle the contributions of AGF and rumen prokaryotes are sorely needed to calculate AGF growth rates and metabolic fluxes to prove this hypothesis and understand its causality for predictable co-culture design.ResultsWe present a simple, microplate-based method to measure AGF and methanogen concentrations in co-culture based on fluorescence and absorbance spectroscopies. Using samples of < 2% of the co-culture volume, we demonstrate significant increases in AGF growth rate and xylan and glucose degradation rates in co-culture with methanogens relative to mono-culture. Further, we calculate significant differences in AGF metabolic fluxes in co-culture relative to mono-culture, namely increased flux through the energy-generating hydrogenosome organelle. While calculated fluxes highlight uncertainties in AGF primary metabolism that preclude definitive explanations for this shift, our method will enable steady-state fluxomic experiments to probe AGF metabolism in greater detail.ConclusionsThe method we present to measure AGF and methanogen concentrations enables direct growth measurements and calculation of metabolic fluxes in co-culture. These metrics are critical to develop a quantitative understanding of interwoven rumen metabolism, as well as the impact of co-culture on polysaccharide degradation and metabolite production. The framework presented here can inspire new methods to probe systems beyond AGF and methanogens. Simple modifications to the method will likely extend its utility to co-cultures with more than two organisms or those grown on solid substrates to facilitate the design and deployment of microbial communities for bioproduction and beyond.
Establishment of a co-culture system using Escherichia coli and Pichia pastoris (Komagataella phaffii) for valuable alkaloid production
Authors: Urui Miya , Yamada Yasuyuki , Ikeda Yoshito , Nakagawa Akira , Sato Fumihiko , Minami Hiromichi , Shitan Nobukazu 
Published: October 2021

Abstract
Background
Plants produce a variety of specialized metabolites, many of which are used in pharmaceutical industries as raw materials. However, certain metabolites may be produced at markedly low concentrations in plants. This problem has been overcome through metabolic engineering in recent years, and the production of valuable plant compounds using microorganisms such as Escherichia coli or yeast cells has been realized. However, the development of complicated pathways in a single cell remains challenging. Additionally, microbial cells may experience toxicity from the bioactive compounds produced or negative feedback effects exerted on their biosynthetic enzymes. Thus, co-culture systems, such as those of E. coli–E. coli and E. coli-Saccharomyces cerevisiae, have been developed, and increased production of certain compounds has been achieved. Recently, a co-culture system of Pichia pastoris (Komagataella phaffii) has gained considerable attention due to its potential utility in increased production of valuable compounds. However, its co-culture with other organisms such as E. coli, which produce important intermediates at high concentrations, has not been reported.

Results
Here, we present a novel co-culture platform for E. coli and P. pastoris. Upstream E. coli cells produced reticuline from a simple carbon source, and the downstream P. pastoris cells produced stylopine from reticuline. We investigated the effect of four media commonly used for growth and production of P. pastoris, and found that buffered methanol-complex medium (BMMY) was suitable for P. pastoris cells. Reticuline-producing E. coli cells also showed better growth and reticuline production in BMMY medium than that in LB medium. De novo production of the final product, stylopine from a simple carbon source, glycerol, was successful upon co-culture of both strains in BMMY medium. Further analysis of the initial inoculation ratio showed that a higher ratio of E. coli cells compared to P. pastoris cells led to higher production of stylopine.

Conclusions
This is the first report of co-culture system established with engineered E. coli and P. pastoris for the de novo production of valuable compounds. The co-culture system established herein would be useful for increased production of heterologous biosynthesis of complex specialized plant metabolites.
UBTF facilitates melanoma progression via modulating MEK1/2-ERK1/2 signalling pathways by promoting GIT1 transcription
Authors: Zhang Jian , Zhang Jiaojiao , Liu Wenli , Ge Rui , Gao Tianyuan , Tian Qiong , Mu Xin , Zhao Lingyu , Li Xu 
Published: October 2021

AbstractBackgroundUBTF is an HMGB-box DNA binding protein and a necessary Pol I/Pol II basal transcription factor. It has been found that UBTF involves in carcinogenesis and progression of a few cancers. Nevertheless, the the biological function and potential molecular mechanism of UBTF in melanoma are still not clear and need to be clarified.MethodsUBTF and GIT1 expressions in melanoma specimens and cell lines were examined by quantitative real-time PCR (qRT-PCR) and Western blot. MTT and colony formation assays were used to investigate the effects of UBTF and GIT1 on melanoma cell proliferation. Cell cycle and apoptosis assays were detected by flow cytometry. Tumor formation assay was used to analyze the effect of UBTF on melanoma growth. Bioinformatics predicting, chromatin immunoprecipitation (ChIP)-qRT-PCR and reporter gene assay were fulfilled for verifing GIT1 as UBTF targeting gene.ResultsHere we reported that UBTF mRNA and protein expressions were upregulated in primary melanoma specimens and cell lines. UBTF overexpression facilitated melanoma cell proliferation and cell cycle progression and restrained. Silencing UBTF suppressed cell multiplication, cell cycle progression and tumor growth, and promoted apoptosis. UBTF expression was positively related with GIT1 expression in human melanoma tissues. It was verified that UBTF promoted GIT1 transcription in melanoma cells through binding to the promoter region of GIT1. Furthermore, GIT1 overexpression promoted melanoma cell growth and suppressed apoptosis. Knockdown of GIT1 inhibited cell multiplication and induced apoptosis. Overexpression of GIT1 eliminated the effects of silencing UBTF on melanoma cells. Importantly, UBTF activated MEK1/2-ERK1/2 signalling pathways by upregulating GIT1 expression.ConclusionsOur study demonstrates that UBTF promotes melanoma cell proliferation and cell cycle progression by promoting GIT1 transcription, thereby activating MEK1/2-ERK1/2 signalling pathways. The findings indicate that UBTF plays a crucial function in melanoma and may be a potential therapeutic target for the treatment of this disease.
Chitosan as possible inhibitory agents and delivery systems in leukemia
Authors: Zivarpour Parinaz , Hallajzadeh Jamal , Asemi Zatollah , Sadoughi Fatemeh , Sharifi Mehran 
Published: October 2021

AbstractLeukemia is a lethal cancer in which white blood cells undergo proliferation and immature white blood cells are seen in the bloodstream. Without diagnosis and management in early stages, this type of cancer can be fatal. Changes in protooncogenic genes and microRNA genes are the most important factors involved in development of leukemia. At present, leukemia risk factors are not accurately identified, but some studies have pointed out factors that predispose to leukemia. Studies show that in the absence of genetic risk factors, leukemia can be prevented by reducing the exposure to risk factors of leukemia, including smoking, exposure to benzene compounds and high-dose radioactive or ionizing radiation. One of the most important treatments for leukemia is chemotherapy which has devastating side effects. Chemotherapy and medications used during treatment do not have a specific effect and destroy healthy cells besides leukemia cells. Despite the suppressing effect of chemotherapy against leukemia, patients undergoing chemotherapy have poor quality of life. So today, researchers are focusing on finding more safe and effective natural compounds and treatments for cancer, especially leukemia. Chitosan is a valuable natural compound that is biocompatible and non-toxic to healthy cells. Anticancer, antibacterial, antifungal and antioxidant effects are examples of chitosan biopolymer properties. The US Food and Drug Administration has approved the use of this compound in medical treatments and the pharmaceutical industry. In this article, we take a look at the latest advances in the use of chitosan in the treatment and improvement of leukemia.
Exosomal transfer of miR-769-5p promotes osteosarcoma proliferation and metastasis by targeting DUSP16
Authors: Liu Wanshun , Wang Binyu , Duan Ao , Shen Kai , Zhang Qi , Tang Xiaolu , Wei Yongzhong , Tang Jian , Zhang Sheng 
Published: October 2021

Abstract
Background
Osteosarcoma (OS) is a malignant tumor originating from mesenchymal stem cells, and has an extremely high fatality rate and ability to metastasize. Although mounting evidence suggests that miR-769-5p is strongly associated with the malignant progression and poor prognosis of various tumors, the exact role of miR-769-5p in OS is still unclear. Therefore, this study aimed to explore the relationship between miR-769-5p and the malignant progression of OS, and its underlying mechanism of action.

Methods
miR-769-5p expression was analyzed in GSE28423 from the GEO database and measured in OS clinical specimens and cell lines. The effects of miR-769-5p on OS proliferation, migration and invasion were measured both in vivo and in vitro. In addition, bioinformatics analyses and luciferase reporter assays were used to explore the target genes of miR-769-5p. Rescue experiments were also conducted. Moreover, a co-culture model was used to test the cell interaction between bone mesenchymal stem cells (BMSC) and OS cells.

Results
We found that miR-769-5p is highly expressed in OS clinical specimens and cell lines. In vivo and in vitro experiments also showed that miR-769-5p significantly promoted the proliferation, migration and invasion of OS cells. Dual-specific phosphatase 16 (DUSP16) was negatively associated with miR-769-5p expression in OS cells and tissue samples and was validated as the downstream target by luciferase reporter assay and western blotting. Rescue experiments showed that DUSP16 reverses the effect of miR-769-5p on OS cells by negatively regulating the JNK/p38 MAPK signaling pathway. Additionally, the results of the co-culture of BMSCs and OS cells confirmed that miR-769-5p was transferred from BMSCs to OS cells through exosomes.

Conclusions
In summary, this study demonstrates for the first time that BMSC-derived exosomal miR-769-5p promotes OS proliferation and metastasis by targeting DUSP16 and activating the JNK/p38 MAPK signaling pathway, which could provide rationale for a new therapeutic strategy for OS.
Cost-effectiveness analysis of integrated community case management delivery models utilizing drug sellers and community health workers for treatment of under-five febrile cases of malaria, pneumonia, diarrhoea in rural Uganda
Authors: Lubogo Patrick , Lukyamuzi John Edward , Kyambadde Deo , Komakech Alex Aboda , Kitutu Freddy Eric , Mulogo Edgar Mugema 
Published: October 2021

AbstractBackgroundMalaria, pneumonia and diarrhoea continue to be the leading causes of death in children under the age of five years (U5) in Uganda. To combat these febrile illnesses, integrated community case management (iCCM) delivery models utilizing community health workers (CHWs) or drug sellers have been implemented. The purpose of this study is to compare the cost-effectiveness of delivering iCCM interventions via drug sellers versus CHWs in rural Uganda.MethodsThis study was a cost-effectiveness analysis to compare the iCCM delivery model utilizing drug sellers against the model using CHWs. The effect measure was the number of appropriately treated U5 children, and data on effectiveness came from a quasi-experimental study in Southwestern Uganda and the inSCALE cross-sectional household survey in eight districts of mid-Western Uganda. The iCCM interventions were costed using the micro-costing (ingredients) approach, with costs expressed in US dollars. Cost and effect data were linked together using a decision tree model and analysed using the Amua modelling software.ResultsThe costs per 100 treated U5 children were US$591.20 and US$298.42 for the iCCM trained-drug seller and iCCM trained-CHW models, respectively, with 30 and 21 appropriately treated children in the iCCM trained-drug seller and iCCM trained-CHW models. When the drug seller arm (intervention) was compared to the CHW arm (control), an incremental effect of 9 per 100 appropriately treated U5 children was observed, as well as an incremental cost of US$292.78 per 100 appropriately treated children, resulting in an incremental cost-effectiveness ratio (ICER) of US$33.86 per appropriately treated U5 patient.ConclusionSince both models were cost-effective compared to the do-nothing option, the iCCM trained-drug seller model could complement the iCCM trained-CHW intervention as a strategy to increase access to quality treatment.
The role of left atrial strain in patients with functional tricuspid regurgitation before and after annuloplasty: a long-term follow-up study
Authors: Meng Qing-long , Meng Hong , Tao Jia , Yang Shu , Wang Hao 
Published: October 2021

Abstract
Background
Functional tricuspid regurgitation (TR) is common among patients with left heart disease and may recur during the follow-up period after selective tricuspid valve annuloplasty (TVA). This study aims to analyse the relationship between left atrial (LA) strain and the degree of preoperative functional TR and to explore the role of LA strain in predicting TR recurrence.

Methods
This study included 63 patients with rheumatic mitral stenosis who underwent mitral valve replacement and concomitant TVA. Additionally, 20 healthy controls were enrolled. Preoperative conventional LA echocardiographic parameters and LA strain were measured. The association between LA strain and preoperative functional TR severity was analysed by Pearson correlation. Predictors of recurrent TR were determined by multivariate logistic regression analyses.

Results
Compared with the control group, the mitral stenosis group developed a significant impairment in terms of LA strain. The degree of preoperative functional TR exhibited moderate correlations with LA reservoir strain (r = − 0.57) and LA conduit strain (r = 0.48). During a median follow-up period of 66.4 ± 36.4 months, TR recurred in 18 patients. Preoperative LA reservoir strain and the mean transmitral gradient were predictors of postoperative TR recurrence. When the two indexes were combined to establish a prediction, the sensitivity and specificity of prediction increased. The area under the receiver operating characteristic curve of the combined indicator was higher than those of the single indicators (0.90 vs. 0.70 and 0.72).

Conclusions
LA strain correlates with preoperative functional TR severity in patients with rheumatic mitral stenosis. The LA reservoir strain and preoperative mean transmitral gradient are independent predictive factors for recurrent TR after TVA.