bluuebunny/crossref_metadata_2025_split huggingface dataset:
Five years’ experience with value-based quality improvement teams: the key factors to a successful implementation in hospital care
Authors: Daniels Kirsten , Rouppe van der Voort Marc B. V. , Biesma Douwe H. , van der Nat Paul B. 
Published: October 2022

Abstract
Background
In recent years, value-based healthcare (VBHC) has become one of the most accepted concepts for fixing the ‘broken’ healthcare systems. Numerous hospitals have embraced VBHC and are trying to implement value-based quality improvement (VBQI) into their practice. However, there is a lack of knowledge on how to practically implement VBHC and organizations differ in their approach. The aim of this study was to explore the main factors that were experienced as hindering and/or supporting in the implementation of VBQI teams in hospital care.

Methods
A qualitative study was performed with semi-structured interviews with 43 members of eight VBQI teams in a large Dutch top-clinical teaching hospital. Participants included physicians, physician assistants, nurses, VBHC project leaders, managers, social workers, researchers and paramedics. Interview grids were structured according to the RE-AIM model (reach, effectiveness, adoption, implementation and maintenance). A thematic content analysis with open coding was used to identify emerging (sub)themes.

Results
We identified nine main factors divided over three domains (organization, culture and practice) that determined whether the implementation of VBQI teams was successful or not: 1). Practical organization of value-based quality improvement teams, 2). Organizational structure 3). Integration of VBHC with existing quality improvement approaches and research 4). Adoption and knowledge of the VBHC concept in the hospital 5). Multidisciplinary engagement 6). Medical leadership 7). Goal setting and selecting quality improvement initiatives 8). Long-cycle benchmarking and short-cycle feedback 9). Availability of outcome data.

Conclusions
Overall, this study goes beyond the general VBHC theory and provides healthcare providers with more detailed knowledge on how to practically implement value-based quality improvement in a hospital care setting. Factors in the ‘organization’ and ‘practice’ domain were mentioned in the strategic value agenda of Porter and Lee. Though, this study provides more practical insight in these two domains. Factors in the ‘culture’ domain were not mentioned in the strategic value agenda and have not yet been thoroughly researched before.
Circadian rhythms in the plant host influence rhythmicity of rhizosphere microbiota
Authors: Newman Amy , Picot Emma , Davies Sian , Hilton Sally , Carré Isabelle A. , Bending Gary D. 
Published: October 2022

AbstractBackgroundRecent studies demonstrated that microbiota inhabiting the plant rhizosphere exhibit diel changes in abundance. To investigate the impact of plant circadian rhythms on bacterial and fungal rhythms in the rhizosphere, we analysed temporal changes in fungal and bacterial communities in the rhizosphere ofArabidopsisplants overexpressing or lacking function of the circadian clock geneLATE ELONGATED HYPOCOTYL(LHY).ResultsUnder diel light–dark cycles, the knock-out mutantlhy-11and the gain-of-function mutantlhy-oxboth exhibited gene expression rhythms with altered timing and amplitude compared to wild-type plants. Distinct sets of bacteria and fungi were found to display rhythmic changes in abundance in the rhizosphere of both of these mutants, suggesting that abnormal patterns of rhythmicity in the plant host caused temporal reprogramming of the rhizosphere microbiome. This was associated with changes in microbial community structure, including changes in the abundance of fungal guilds known to impact on plant health. Under constant environmental conditions, microbial rhythmicity persisted in the rhizosphere of wild-type plants, indicating control by a circadian oscillator. In contrast, loss of rhythmicity inlhy-oxplants was associated with disrupted rhythms for the majority of rhizosphere microbiota.ConclusionsThese results show that aberrant function of the plant circadian clock is associated with altered rhythmicity of rhizosphere bacteria and fungi. In the long term, this leads to changes in composition of the rhizosphere microbiome, with potential consequences for plant health. Further research will be required to understand the functional implications of these changes and how they impact on plant health and productivity.
HP1a-mediated heterochromatin formation promotes antimicrobial responses against Pseudomonas aeruginosa infection
Authors: Wu Po-Jen , Yan Shian-Jang 
Published: October 2022

Abstract
Background
Pseudomonas aeruginosa is a Gram-negative bacterium that causes severe infectious disease in diverse host organisms, including humans. Effective therapeutic options for P. aeruginosa infection are limited due to increasing multidrug resistance and it is therefore critical to understand the regulation of host innate immune responses to guide development of effective therapeutic options. The epigenetic mechanisms by which hosts regulate their antimicrobial responses against P. aeruginosa infection remain unclear. Here, we used Drosophila melanogaster to investigate the role of heterochromatin protein 1a (HP1a), a key epigenetic regulator, and its mediation of heterochromatin formation in antimicrobial responses against PA14, a highly virulent P. aeruginosa strain.

Results
Animals with decreased heterochromatin levels showed less resistance to P. aeruginosa infection. In contrast, flies with increased heterochromatin formation, either in the whole organism or specifically in the fat body—an organ important in humoral immune response—showed greater resistance to P. aeruginosa infection, as demonstrated by increased host survival and reduced bacterial load. Increased heterochromatin formation in the fat body promoted the antimicrobial responses via upregulation of fat body immune deficiency (imd) pathway-mediated antimicrobial peptides (AMPs) before and in the middle stage of P. aeruginosa infection. The fat body AMPs were required to elicit HP1a-mediated antimicrobial responses against P. aeruginosa infection. Moreover, the levels of heterochromatin in the fat body were downregulated in the early stage, but upregulated in the middle stage, of P. aeruginosa infection.

Conclusions
These data indicate that HP1a-mediated heterochromatin formation in the fat body promotes antimicrobial responses by epigenetically upregulating AMPs of the imd pathway. Our study provides novel molecular, cellular, and organismal insights into new epigenetic strategies targeting heterochromatin that have the potential to combat P. aeruginosa infection.
Endoplasmic reticulum-quality control pathway and endoplasmic reticulum-associated degradation mechanism regulate the N-glycoproteins and N-glycan structures in the diatom Phaeodactylum tricornutum
Authors: Chen Jichen , Du Hong , Liu Zidong , Li Tangcheng , Du Hua , Wang Wanna , Aslam Muhammad , Chen Weizhou , Li Ping , Luo Haodong , Fang Hao , Liu Xiaojuan 
Published: October 2022

AbstractTunicamycin inhibits the first step of protein N-glycosylation modification. However, the physiological, transcriptomic, and N-glycomic effects of tunicamycin on important marine diatom Phaeodactylum tricornutum are still unknown. In this study, comprehensive approaches were used to study the effects of tunicamycin stress. The results showed that cell growth and photosynthesis were significantly inhibited in P. tricornutum under the tunicamycin stress. The soluble protein content was significantly decreased, while the soluble sugar and neutral lipid were dramatically increased to orchestrate the balance of carbon and nitrogen metabolisms. The stress of 0.3 μg ml−1 tunicamycin resulted in the differential expression of ERQC and ERAD related genes. The upregulation of genes involved in ERQC pathway, the activation of anti-oxidases and the differential expression of genes related with ERAD mechanism might be important for maintaining homeostasis in cell. The identification of N-glycans, especially complex-type N-glycan structures enriched the N-glycan database of diatom P. tricornutum and provided important information for studying the function of N-glycosylation modification on proteins. As a whole, our study proposed working models of ERQC and ERAD will provide a solid foundation for further in-depth study of the related mechanism and the diatom expression system.
A review on the role of cyclin dependent kinases in cancers
Authors: Ghafouri-Fard Soudeh , Khoshbakht Tayyebeh , Hussen Bashdar Mahmud , Dong Peixin , Gassler Nikolaus , Taheri Mohammad , Baniahmad Aria , Dilmaghani Nader Akbari 
Published: October 2022

AbstractThe Cyclin-dependent kinase (CDK) class of serine/threonine kinases has crucial roles in the regulation of cell cycle transition and is mainly involved in the pathogenesis of cancers. The expression of CDKs is controlled by a complex regulatory network comprised of genetic and epigenetic mechanisms, which are dysregulated during the progression of cancer. The abnormal activation of CDKs results in uncontrolled cancer cell proliferation and the induction of cancer stem cell characteristics. The levels of CDKs can be utilized to predict the prognosis and treatment response of cancer patients, and further understanding of the function and underlying mechanisms of CDKs in human tumors would pave the way for future cancer therapies that effectively target CDKs. Defects in the regulation of cell cycle and mutations in the genes coding cell-cycle regulatory proteins lead to unrestrained proliferation of cells leading to formation of tumors. A number of treatment modalities have been designed to combat dysregulation of cell cycle through affecting expression or activity of CDKs. However, effective application of these methods in the clinical settings requires recognition of the role of CDKs in the progression of each type of cancer, their partners, their interactions with signaling pathways and the effects of suppression of these kinases on malignant features. Thus, we designed this literature search to summarize these findings at cellular level, as well as in vivo and clinical levels.
Combined association of triglyceride-glucose index and systolic blood pressure with all-cause and cardiovascular mortality among the general population
Authors: Yu Yu , Gu Min , Huang Hao , Cheng Sijing , Deng Yu , Cai Chi , Chen Xuhua , Niu Hongxia , Ning Xiaohui , Hua Wei 
Published: October 2022

AbstractBackgroundThe combined association of triglyceride-glucose (TyG) index and different systolic blood pressure (SBP) levels with all-cause and cardiovascular mortality among the general population remains unclear.MethodsIn this study, 6245 individuals were from the National Health and Nutrition Examination Survey (1999–2002). The study endpoints were all-cause and cardiovascular mortality. Multivariate Cox proportional hazards regression models were used to explore the combined association of TyG index and different SBP levels with all-cause and cardiovascular mortality.ResultsDuring a mean follow-up period of 66.8 months, a total of 284 all-cause deaths (331/100000 person-years) and 61 cardiovascular deaths (66/100000 person-years) were recorded. Multivariate Cox regression analysis revealed that the combination of low TyG index and low SBP (< 120 mmHg and < 130 mmHg) was associated with a reduced risk of all-cause and cardiovascular mortality than others. However, survival benefit was not observed in the combined group with the low TyG index and SBP < 140 mmHg. Furthermore, the mortality rate in the combined group of low TyG index and low SBP gradually increased with the elevation of SBP level.ConclusionThe combination of low TyG index and low SBP (< 120 mmHg and < 130 mmHg) was associated with a lower risk of all-cause and cardiovascular mortality. However, no survival benefit was observed in the combined group of low TyG index and SBP < 140 mmHg.
Integrative analysis of m3C associated genes reveals METTL2A as a potential oncogene in breast Cancer
Authors: Wang Shuai , Li Huiting , Liu Jiheng , Zhang Qianqian , Xu Wei , Xiang Juanjuan , Fang Li , Xu Ping , Li Zheng 
Published: October 2022

AbstractRNA methylation modifications, especially m6A mRNA modification, are known to be extensively involved in tumor development. However, the relationship between N3-methylcytidine (m3C) related genes and tumorigenesis has rarely been studied. In this research, we found that m3C-related genes were expressed at different levels and affected patients’ prognosis across multiple cancer types from The Cancer Genome Atlas and multi-omics levels. Importantly, methyltransferase-like proteins 2A (METTL2A) had a high amplification frequency (~ 7%) in patients with breast invasive carcinoma (BRCA), and its overexpression was an independent predictor of poor overall survival. Enrichment analysis of associated genes revealed that METTL2A may activate DNA synthesis and cell proliferation pathways in BRCA cells. Through drug sensitivity analysis, Trifluridine, PD407824, and Taselisib were shown to be effective drugs for METTL2A-positive BRCA patients. Overall, our research conducts a holistic view of the expression level and prognostic signature of m3C-related genes with multiple malignancies. Importantly, METTL2A has been intensely explored as a potential oncogene in BRCA, to aid the development of potential drug agents for precision therapy in breast cancer patients.
HPV 16 E7 alters translesion synthesis signaling
Authors: Wendel Sebastian O. , Stoltz Avanelle , Xu Xuan , Snow Jazmine A. , Wallace Nicholas 
Published: October 2022

AbstractA subset of human papillomaviruses (HPVs) are the cause of virtually every cervical cancer. These so-called “high-risk” HPVs encode two major oncogenes (HPV E6 and E7) that are necessary for transformation. Among "high-risk” HPVs, HPV16 causes most cervical cancers and is often used as a representative model for oncogenic HPVs. The HPV16 E7 oncogene facilitates the HPV16 lifecycle by binding and destabilizing RB, which ensures the virus has access to cellular replication machinery. RB destabilization increases E2F1-responsive gene expression and causes replication stress. While HPV16 E6 mitigates some of the deleterious effects associated with this replication stress by degrading p53, cells undergo separate adaptations to tolerate the stress. Here, we demonstrate that this includes the activation of the translesion synthesis (TLS) pathway, which prevents replication stress from causing replication fork collapse. We show that significantly elevated TLS gene expression is more common in cervical cancers than 15 out of the 16 the other cancer types that we analyzed. In addition to increased TLS protein abundance, HPV16 E7 expressing cells have a reduced ability to induct a critical TLS factor (POLη) in response to replication stress-inducing agents. Finally, we show that increased expression of at least one TLS gene is associated with improved survival for women with cervical cancer.
Whether individualized dose escalation should be recommended for lymph nodes with different sizes in the definitive radiotherapy of cervical cancer?
Authors: Lv Xiaojuan , Rao Huiting , Feng Tao , Wu Chufan , Lou Hanmei 
Published: October 2022

Abstract
Background and purpose
Dose escalation for positive node maybe improve the regional control of patients with node-positive cervical cancer, but the optimal dose for nodes of different sizes remains controversial. The purpose of this study was to explore the individualized dose escalation for lymph nodes (LNs) with different sizes in the definitive radiotherapy of cervical cancer.

Methods
A total of 1002 cervical cancer patients with the International Federation of Gynecology and Obstetrics (FIGO 2009) stage IB1–IVA, who were treated by definitively radiotherapy between September 2013 and December 2016 were enrolled. All LNs identified by computed tomography/magnetic resonance imaging (CT/MRI) were assigned into three groups according to the short diameters of < 1 cm, 1–2 cm or ≥ 2 cm at pretreatment.

Results
In total, 580 patients with 1310 LNs were detected. The nodal control rate in groups of LNs < 1 cm, 1–2 cm and ≥ 2 cm was 99.4%, 96%, and 75.9%, respectively (P = 0.000). Among LNs < 1 cm, the control, overall survival (OS) and progression-free survival (PFS) rates did not significantly differ among three dose-based groups (≤ 50.4 Gy, 50.4–60 Gy, > 60 Gy) (control rate, 99.4% vs. 99.3% vs. 100%, P = 0.647) (5-year OS, 76.2% vs. 79% vs. 81.6%, P = 0.682) (5-year PFS, 74.1% vs. 73.9% vs. 78.9% P = 0.713). Among LNs of 1–2 cm, the control and PFS rates were significantly higher in the group of dose ≥ 55 Gy than the group of dose < 55 Gy (control rate, 98% vs. 93.6%, P = 0.028) (5-year PFS, 69.6% vs. 56.7%, P = 0.025). However, this did not cause a significant difference for 5-year OS rate (72.6% vs. 68.3%, P = 0.5). Among LNs ≥ 2 cm, the control, OS, and PFS rates were higher in the group of dose ≥ 55 Gy than the group of dose < 55 Gy, while no significant difference was found (control rate, 82.1% vs. 63.2%, P = 0.107) (5-year OS, 60.6% vs. 37.5%, P = 0.141) (5-year PFS, 51.5% vs.37.5%, P = 0.232).

Conclusions
Radiation dose escalation is not necessary for LNs < 1 cm, and dose escalation of 55 Gy is enough for LNs of 1–2 cm.
LncRNA CASC9 promotes cell proliferation and invasion in osteosarcoma through targeting miR-874-3p/SOX12 axis
Authors: Qiu Haiyan , Yang Di , Li Xiaolin , Feng Fabo 
Published: October 2022

Abstract
Background
Osteosarcoma (OS) is a common primary malignant bone tumor. This study aimed to explore the biological role of long on-coding RNA (lncRNA) CASC9 and its regulatory mechanism in OC.

Methods
The CASC9 expressions in OS cells and tissues were measured using qRT-PCR. The functional role of CASC9 in OC was studied using MTT assay, colony formation assay, transwell invasion assay, and xenograft tumor assay. In addition, the mechanism of CASC9 function was determined using luciferase reporter assay. Western blot was used to analyze protein expressions in our paper.

Results
LncRNA CASC9 was found to be up-regulated in OS. Knockdown of CASC9 inhibited the proliferation and invasion of OS cells. Besides, miR-874-3p was identified as the target of CASC9, and SOX12 acted as a potential target of miR-874-3p. The down-regulation of miR-874-3p recovered the reduction in cell invasion and proliferation in vitro which were induced by CASC9 knockdown and delayed the tumor progression in vivo.

Conclusion
LncRNA CASC9 promotes cell proliferation and invasion in OS via miR-874-3p/SOX12 axis. Our study might provide novel biomarkers and potential therapeutic targets for OS treatment.
Effect of different feeding methods on gastrointestinal function in critical patients (DFM-GFC): study protocol for a randomized controlled trial
Authors: Yang Guang , Deng Aijing , Zheng Bojun , Li Jian , Yu Yi , Ouyang Honglian , Huang Xin , Chen Hong 
Published: October 2022

Abstract
Background
Enteral nutrition is a major pathway of nutrition for patients requiring critical care. However, it remains unclear whether intermittent or continuous feeding is the better approach, especially after nasogastric enteral nutrition via a gastric tube. Therefore, this randomized controlled clinical study was designed to observe the effects of different methods on critically ill patients.

Methods
Different Feeding Methods on Gastrointestinal Function of Critical patients (DFM-GFC) is a randomized clinical study that will be performed to assess the effects of three feeding methods on critically ill patients. A total of 90 critically ill patients will be equally randomized into three groups: continuous feeding, cyclic feeding, and intermittent feeding. The patients will be administered a gastrointestinal nutrition preparation over 24 h via a gastric tube or over 16 h via an intermittent pump. The primary outcome is the mean duration (days) to reach the caloric goal in each group. Secondary outcomes include the rate of onset of gastric residual, abdominal pressure, the rate of onset pneumonia, and the proportion of individuals achieving the caloric goal. Additionally, the length of intensive care unit (ICU) stay and mortality rate at 28 days post-enrolment will be evaluated.

Discussion
This study will observe the effects of different feeding methods on various parameters, such as the energy target and gastrointestinal motility, in critically ill patients to improve quality of life and reduce the case fatality rate. The purpose of this study is to explore whether there is a more effective, safer and cost-efficient feeding method for the clinical treatment of critically ill patients.

Trial registration
ID: NCT04224883, ClinicalTrials.gov, registered January 9, 2020
Understanding the perspectives of recruiters is key to improving randomised controlled trial enrolment: a qualitative evidence synthesis
Authors: Farrar Nicola , Elliott Daisy , Houghton Catherine , Jepson Marcus , Mills Nicola , Paramasivan Sangeetha , Plumb Lucy , Wade Julia , Young Bridget , Donovan Jenny L. , Rooshenas Leila 
Published: October 2022

Abstract
Background
Recruiting patients to randomised controlled trials (RCTs) is often reported to be challenging, and the evidence base for effective interventions that could be used by staff (recruiters) undertaking recruitment is lacking. Although the experiences and perspectives of recruiters have been widely reported, an evidence synthesis is required in order to inform the development of future interventions. This paper aims to address this by systematically searching and synthesising the evidence on recruiters’ perspectives and experiences of recruiting patients into RCTs.

Methods
A qualitative evidence synthesis (QES) following Thomas and Harden’s approach to thematic synthesis was conducted. The Ovid MEDLINE, CINAHL, EMBASE, PsycInfo, Cochrane Central Register of Controlled Trials, ORRCA and Web of Science electronic databases were searched. Studies were sampled to ensure that the focus of the research was aligned with the phenomena of interest of the QES, their methodological relevance to the QES question, and to include variation across the clinical areas of the studies. The GRADE CERQual framework was used to assess confidence in the review findings.

Results
In total, 9316 studies were identified for screening, which resulted in 128 eligible papers. The application of the QES sampling strategy resulted in 30 papers being included in the final analysis. Five overlapping themes were identified which highlighted the complex manner in which recruiters experience RCT recruitment: (1) recruiting to RCTs in a clinical environment, (2) enthusiasm for the RCT, (3) making judgements about whether to approach a patient, (4) communication challenges, (5) interplay between recruiter and professional roles.

Conclusions
This QES identified factors which contribute to the complexities that recruiters can face in day-to-day clinical settings, and the influence recruiters and non-recruiting healthcare professionals have on opportunities afforded to patients for RCT participation. It has reinforced the importance of considering the clinical setting in its entirety when planning future RCTs and indicated the need to better normalise and support research if it is to become part of day-to-day practice.

Trial registration
PROSPERO CRD42020141297 (registered 11/02/2020).