bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of Consolidated Framework for Implementation Research to Improve Clostridioides difficile Infection Management in South African District Hospitals
Authors: Legenza Laurel , Coetzee Renier , Rose Warren E. , Esack Tasneem , Crombie Kenneth , Mina Megan , Safdar Nasia , Barnett Susanne G. 
Published: June 2021

Abstract
Background

Clostridioides difficile infection (CDI) is a global health threat. Measurable gaps exist in CDI quality of care and CDI knowledge in South Africa. This study describes the development of a CDI intervention informed by the local context within South African public district level hospitals, and analyzes the CDI intervention development, implementation process and adaptations to understand acceptance, uptake, successes, and failures of the CDI intervention.
Methods

A CDI checklist intervention was designed and implemented at three district level hospitals in the Western Cape, South Africa. The Consolidated Framework for Implementation Research (CFIR) was used as a framework to contextualize study findings, including a description of the implementation process and adaptations for each hospital. A mixed-methods approach was applied with quantitative outcomes data and qualitative interview and focus group data with front-line and administrative healthcare personnel. Transcripts were coded to a priori workflow steps as well as to aspects of the CDI checklist intervention and emerging themes. The CFIR framework was applied to results from the qualitative interviews, observations by research team members, and quantitative patient outcomes data in order to identify drivers and barriers to implementation and to understand differences in uptake at the three sites. Highly relevant and moderately relevant constructs for the Intervention, Inner Setting, and Implementation Process domains were identified.
Results

Each hospital adapted the implementation process based on available resources, while maintaining the intervention core elements. One hospital displayed high uptake of the intervention compared to the two other hospitals. Highly relevant CFIR constructs linked to intervention uptake included tension for change, strong peer intervention champions, champions in influential leadership positions, and intervention complexity, among others. Tension of change at the high uptake hospital was also supported by an academic partnership for antimicrobial stewardship.
Conclusion

We provide a straight-forward health systems strengthening intervention for CDI that is both needed and uncomplicated, in an understudied LMIC setting. Intervention uptake was highest in the hospital with tension for change, influential champions, and existing academic partnerships. Further research is needed in reaching and involving understudied settings with fewer academic connections and to examine impact on patient outcomes.
Research on the Dynamics and Evolution of Regional Blue-green Space Driven by the Development of World-class Urban Agglomerations
Authors: Pan Ziwu , Zhu Jun , Liu Zhenzhen , Qin Fen 
Published: June 2021

Abstract
In recent years, the process of urbanization in China has accelerated, and changes in the underlying surface have caused the difference in average temperature between built-up areas and suburbs to increase, resulting in an urban heat island effect, which has become an important environmental issue for today's urban sustainable development. The Yangtze River Delta urban agglomeration region is the fastest-growing region in China, with economically developed and populous cities such as Shanghai, Nanjing and Suzhou. It has become one of the six major urban agglomerations in the world, and its heat island effect is particularly prominent. The single urban heat island phenomenon gradually evolves into the urban agglomeration heat island phenomenon with urbanization. However, the dynamic transfer process of key blue-green space landscapes that can alleviate land surface temperature (LST) and regional thermal environment (RTE) is still poorly understood, especially in the context of urban agglomerations. With the approval of the State Council on the development plan of the Huaihe River Ecological Economic Belt, the construction of which has been officially upgraded to a national strategy. The Eastern HaiJiang River and Lake Linkage Zone (EJRLLZ) emphasizes strengthening the docking and interaction with the surrounding areas such as the Yangtze River Delta and the Wanjiang City Belt. With the diffusion of the heat island effect of the Yangtze River Delta urban agglomeration, as one of the areas with great potential development around the world-class urban agglomeration, the rich water body and green space in the ERLLZ area are also destroyed and affected. Therefore, we take this region as a case to further quantify the impact of urbanization and urban agglomeration development on the dynamics and evolution of blue-green space.
Adipose Tissue Derived Mesenchymal Stem Cells (ADMSCs) Protect Against Hyperglycemia and Hyperlipidemia Induced Heart Failure by Inhibiting Autophagy Related Apoptosis
Authors: Xu Xu , Qiang Sujing , Tao Lingyun , Zhou Jie , Ni Jing 
Published: June 2021

Abstract
Background

Mesenchymal stem cells (MSCs), kinds of seed cells, are expected to improve impaired diabetic cardiac function. Inflammation and autophagy play the important role in the development of metabolic disorder induced heart failure. The aim of this work was to assess the effect of adipose tissue derived mesenchymal stem cells (ADMSCs) on metabolic disorder induced heart failure and the underlying mechanisms.
Methods

In vivo, 8 weeks old male C57BL/6 mice were randomly divided into three groups: normal chaw mice (sham group), high fat diet fed and streptozotocin intraperitoneal injected mice (HFD + STZ group) and ADMSCs tail intravenous injected per week for 3 months after the mice were treated with HFD + STZ (ADMSCs + HFD + STZ group). The lipid and glucose levels as well as echocardiography were measured per week. Immunohistochemistry was used to detect the adhesion of macrophages in heart tissue among three groups. Besides, inflammatory cytokines such as interleukin-1β (IL-1β), tumor necrosis factor α (TNFα), interleukin-6 (IL-6) and interleukin-8(CXCL-15) were measured by western blot or RT-qPCR. In vitro, H9c2 cardiomyocytes were stimulated to 33mM glucose in the presence or absence of IL-1β. Transmission electron microscope, mRFG-GFP-LC3 assay and flow cytometry were used to investigate autophagy related apoptosis in H9c2 cells.
Results

HFD + STZ treated mice presented significant cardiac hypertrophy, body weight loss, hyperglycemia and hyperlipidemia. However, these changes were remarkably reversed by ADMSCs administration. The administration of ADMSCs also remit histological alterations and deposition of collagen in the heart tissue. Furthermore, ADMSCs downregulated the adhesion of macrophages in heart tissue. More importantly, IL-1β from macrophages increased the autophagy of myocardial cell stimulated with high glucose which eventually leaded to their apoptosis and the following cardiac dysfunction.
Conclusions

This study confirmed that ADMSCs may have potential for use in improving cardiac function by restraining autophagy and apoptosis of myocardial cell. We also found the roles of the IL-1β in hyperglycemia and hyperlipidemia induced cardiac injuries, which may be a key factor for diabetic complications.
The Heart has Intrinsic Ketogenic Capacity that is Facultatively Upregulated in Heart Failure with Preserved Ejection Fraction
Authors: O'Sullivan John , Koay Yen Chin , Cao Yang , Bai Angela Yu , Lal Sean , Lusis Aldons , Kaye David , Larance Mark 
Published: June 2021

Abstract
Heart Failure with preserved Ejection Fraction or ‘HFpEF’ is now the most common type of heart failure worldwide, with considerable morbidity and mortality, and with no effective pharmacotherapies. For the first time, we show that the human and murine HFpEF heart have impaired uptake of ketone bodies, and reveal an intrinsic capacity of human and murine hearts to generate their own ketones via the canonical rate-limiting ketogenic enzyme, 3-hydroxy-3-methylglutaryl CoA synthase 2 (HMGCS2). We demonstrate that protein levels of HMGCS2 are dramatically elevated in HFpEF myocardium that does not overcome reduced specific activity of this enzyme. This appeared to be due to hyperacetylation caused by depletion of the de-acetylating enzyme sirtuin 3 and decreased oxidized/reduced nicotinamide adenine dinucleotide (NAD+/NADH) ratio, upon which the deacetylation activity of sirtuins is dependent. Also for the first time, we show that the canonical stimuli that serve to turn on ketogenesis in the liver are present locally in the HFpEF heart, augmented by a profound energy deficiency as determined by depleted phosphocreatine/ adenosine triphosphate (PCr/ATP) ratio. Thus, metabolically inflexible HFpEF hearts try to auto-regulate their energy supply by upregulating ketogenesis as an apparent “rescue strategy”. These results serve to reframe our understanding of cardiac ketone metabolism and open opportunities for novel therapeutic strategies for HFpEF, urgently needed.
Hydrostatic Pressure Regulates Microbial Structuring And Metabolic Functions In The Pelagic Ocean
Authors: Liu Ying , Zeng Mengchu , Xie Zhe , Ning Daliang , Zhou Jizhong , Yu Xi , Liu Rulong , Zhang Li , Fang Jiasong 
Published: June 2021

Abstract
Background: Microbial-mediated decomposition of particulate organic matter (POM) during its downward transport from the surface to the deep ocean constitutes a critical component of the global ocean carbon cycle. However, the extent to which hydrostatic pressure affects microbial community structuring and metabolic functions is largely underexplored. Results: In this study, we investigated microbial community succession, phylogenetic and functional diversity, and metabolic capabilities during POM decomposition by particle-attached (PAM) and free-living microorganisms (FLM) under increasing hydrostatic pressures. Diatom-originated 13C-labeled POM was used to incubate surface water microbial communities from the East China Sea (ECS) at pressures of 0.1, 20, and 40 MPa (megapascal). Our results showed that the PAM and FLM communities exhibited contrasting patterns and pressure-dependencies in diversity, richness, and evenness. Microbial assembly was governed predominantly by stochastic processes at low pressure and by deterministic processes at high pressure. Network analysis uncovered the non-randomly structured PAM and FLM communities and clusters of operational taxonomic units (OTUs) that reflected different functional and ecological capacities of the subgroups. Metatranscriptomic analysis revealed that gene expression of known metabolic pathways (carbohydrate, amino acid, and energy production) varied greatly with pressure and between PAM and FLM. Furthermore, the FLM communities maintained higher metabolic activities than the PAM communities at high pressures, indicating the apparent difference in resource utilization capacity and ecological functions of PAM and FLM in different pelagic zones of the ocean. Overall, we demonstrated that marine heterotrophic microbial assemblage patterns were non-random; the PAM were crucial in community structuring, whereas the FLM played more important roles in POM decomposition in the deep. Conclusions: Our results provide detailed insights into and increased mechanistic understanding of the structuring and succession of microbial communities and metabolic functions associated with POM degradation in the pelagic ocean.
Glycyrrhiza Uralensis Promote the Metabolism of Toxic Components of Aconitum Carmichaeli by CYP3A and Alleviate the Development of Chronic Heart Failure
Authors: Ni Lulu , Wan Fang , Li Jiangan , Ai Min , Kong Lingzhong , Miao Ping , Tu Su 
Published: June 2021

Abstract
BackgroundCHF is a common clinical critical disease with high mortality and short survival. Aconitum, as "the first drug of choice for invigorating Yang and saving lives", has been widely used for the treatment of heart failure. However, toxic components of Aconitum can easily lead to serious arrhythmia, respiratory depression, shock and even death [1, 2]. ObjectiveTo investigate the mechanisms of Glycyrrhizae reducing the toxicity of Aconitum.Method A High Performance Liquid Chromatography (HPLC) method for the determination of aconitine (AC), mesaconitine (MA) and hypaconitine (HA) was established; The effect of Glycyrrhiza on CYP3A1 / 2 mRNA expression was detected by RT-PCR; SD rats were given Aconitum and compatibility of Glycyrrhizae and Aconitum by gavage respectively, the blood concentration of toxic components were determined by LC-MS / MS; The CHF rat model was established by intraperitoneal injection of adriamycin (2.5 mg / kg), and were randomly divided into model, Aconitum, the compatibility of Glycyrrhizae and Aconitum and Captopril group. After 4 weeks of gavage, the levels of BNP, Ang II and ALD in blood were detected by ELISA, and the contents of adenosine monophosphate (ATP, ADP and AMP) in myocardium were determined by HPLC.Result AC, MA and HA produced three, three and two metabolites respectively; Ketoconazole significantly inhibited the metabolites of AC, MA and HA; Glycyrrhiza induced CYP3A gene expression, and significantly promoted the metabolism of toxic components of Aconitum; The level of ALD in the compatibility of Glycyrrhizae and Aconitum group was significantly lower than that in Aconitum group. After intervention with the compatibility of Glycyrrhizae and Aconitum, ATP increased significantly, ADP decreased significantly.Conclusion Glycyrrhiza promoted the metabolism of toxic components of Aconitum by up regulating the expression of CYP3A, and reduced the content of BNP, Ang II and ALD, improved the energy metabolism disorder of myocardium, alleviated the development of CHF.
Grazed rain-fed small-grain cereals as a forage option for small-scale dairy systems in central Mexico
Authors: Vega-García Jesús Israel , López-González Felipe , Morales-Almaraz Ernesto , Arriaga-Jordán Carlos Manuel 
Published: June 2021

Abstract
Small-scale dairy systems face reduced availability of water for irrigation of pastures and disruption in the amount or pattern of rains due to climate change, so research on alternative short-cycle rain-fed forages is needed. Grazing reduces feeding costs and small-grain cereals may be an option. The objective was to assess on-farm the performance of dairy cows grazing 6 h/d of three small-grain cereals: rye (RYE), wheat (WHT), and triticale (TRT), and supplemented 4.5 kg DM/cow/d of concentrate. Twelve Holstein cows were used in repeated 3x3 Latin Squares with 14-day experimental periods. Pasture variables were analysed with a split-plot design, and economic analysis was performed with partial budgets. Sampling of forage (sward height, net herbage accumulation, botanical and chemical composition of herbage) and animal variables (milk yield and composition, live weight, and body condition score) were at the end of each period. RYE showed a trend (P = 0.10) for higher net herbage accumulation with highly significant differences (P < 0.001) among periods. RYE had higher DM, a lower CP content (P < 0.05) and no differences for other chemical components between treatments (P > 0.05). RYE proportion in pasture was consistently higher, whilst the lowest cereal proportion was in WHT. There were no differences (P > 0.05) for any animal variable. The RYE and TRT treatments proved useful as rain-fed forage alternatives under grazing. WHT showed lower crop and economic performance. However given the higher cereal component in pastures, regrowth potential, post-grazing herbage mass, as well as better economic performance, the RYE treatment was better ranked by the participating farmer.
Asymptomatic Bacteriuria Among Pregnant Women in Debre Markos, Ethiopia: Prevalence, Risk Factors, and Antimicrobial Susceptibility of Isolates
Authors: Addis Yihunalem , Biset Sirak , Gizachew Mucheye 
Published: June 2021

Abstract
In low-income countries, asymptomatic bacteriuria (ASB) during pregnancy is a major cause for both maternal and foetal health risks. Rapid emergence of antimicrobial resistance also needs continuous monitoring of susceptibility profiles of uropathogens. We conducted a hospital-based cross-sectional study to deterimne prevalence, antimicrobial susceptibility, and associated risk factors of ASB among pregnant women. Socio-demographic and clinical data were collected by interview and extracted from women's medical records. Identification of bacteria from urine, and their susceptibility tests were done by using recommended methods. Logistic regression analyses were done by SPSS versions 20. The p-value <0.05 at 95% CI was considered as statistically significant. Of the 172 study participants, 24 (14%) had ASB. Among 24 isolates, 13 (54.2%) were gram-negative, and of these, E. coli (8; 61.5%) was predominant followed by K. pneumoniae (4; 30.8%). Previous UTI and antibiotic use were significantly associated risk factors for ASB. E .coli, S. areus and CoNS were resistant to tetracycline (87.5%), cotrimoxazole (83.3%), and gentamycin (80%), respectively. Prevalence of ASB was lower than many previous reports in the country. Commonly used antibiotic susceptibility profiles of isolates were known. Hence, hard work ought to assume to decline the consequence of ASB and antibiotics resistance.
Effects of Gastrodin on Analgesia and Inhibition of Ferroptosis
Authors: Wang JinYue , He Zhixian , Liu Xin , Wang Xing 
Published: June 2021

Abstract
Background: Gastrodin possesses low toxicity and a broad range of pharmacological activities and exhibits beneficial effects in neurological diseases. This study investigated the effects of gastrodin (GAS) on analgesic, anti-inflammatory, anxiolytic and inhibition of ferroptosis. Materials and Methods: The chronic inflammatory pain model of C57BL/6J mice was established by hindpaw injection of complete Freund’s adjuvant (CFA). After GAS treatment, Thermal hyperalgesia test, Mechanical allodynia test, Elevated plus-maze (EPMT) and Open-field test (OFT) were performed to assess the behavioral changes of pain and anxiety. mRNAs of FTHI, GPX4, HO-1 and PTGS2 were measured by RT-qPCR. Results: In CFA-injected C57BL/6 mice, we found that the mechanical and thermal pain threshold was increased with treatment of GAS. In EPMT, the number of entries in open arms and retention times of open arms were increased by GAS. In the OFT, the time spent in the central area was also increased. Furthermore, GAS enhanced mRNA expressions of FTHI, GPX4 and H0-1, as well as decreased the expression of PTGS2 in a dose-dependent manner. Conclusion: GAS is effective in the treatment of mice chronic inflammatory pain and anxiety-like behaviors. It maybe exhibit potential neuroprotective effects through inhibition of ferroptosis.
Concomitant of Proton Pump Inhibitors is Associated with Poor Clinical Outcomes in Patients Treated with Immune Checkpoint Inhibitors ：An Up-to-date Systematic Review and Meta-analysis
Authors: Mao Haiyan , Tong Jiandong , Yan Xuebing , Liu Chaoxing , Yang Mengxue , Guo Huaijuan 
Published: June 2021

Abstract
Background: The emergence of immune checkpoint inhibitors has greatly changed the treatment outcome of advanced malignant tumors. The basic medication for patients with advanced solid tumors may affect the efficacy of immunotherapy. The use of proton pump inhibitors may change the acidic environment and inhibit intestinal flora, thereby affecting the efficacy of immunotherapy. To clarify the correlation between PPI administration and the prognosis of solid cancer patients treated with ICI, we conducted a meta-analysis.Method: Before February 12th, 2021, PubMed, Cochrane Library, Web of Science and EMBASE databases were used to search for eligible documents. The association of PPI administration with overall survival (OS) and progression-free survival (PFS), hazard ratio (HR) and 95% confidence interval (CI) were determined.Results: This study included 10 studies, a total of 4072 patients with solid cancer who received ICI treatment. Overall, the PPI administered with OS (HR=1.31 (1.11-1.52), P = 0.001) deteriorate significantly associated. In the subgroup analysis based on cancer type, PPI administration was associated with worsening of PFS in NSCLC, and better results of PFS in melanoma patients. In addition, between 30 days before the occurrence of ICI and 30 days after the occurrence of ICI, PPI administration may reduce the efficacy of ICI. Conclusion: Patients with solid cancer receiving ICI should use PPI with caution. However, only poor statistical results are observed on the OS, and further verification is still essential. This study was registered in PROSPERO with registration number CRD42021243707.
Cis-clustering of cadherin-23 controls the kinetics of cell-cell adhesion
Authors: Rakshit Sabyasachi , Srini Cheerneni , Singaraju Gayathri , Arora Nisha , Das Sayan , Sagar Amin , Kumar Anuj 
Published: June 2021

Abstract
Cis and trans-interactions in cadherins are the foundations of cellular adhesions in multicellular organisms. While the trans-interactions mediate the intercellular attachment, the cis-interaction is presumed as reinforcement to trans. Thus, trans precedes cis has been the well-accepted model in cadherin adhesion. The stronger affinity of trans-binding over cis has been the decisive influence in the trans first model. Here we show that cadherin-23, a non-classical cadherin with an extended extracellular region, can undergo cis-clustering in solution independent of trans and phase separate as liquid droplets. Using single-molecule measurements, we decipher that weaker cis-interactions favor the cis-clustering. In-cellulo, the cis-clustering is manifested as puncta, a common feature in non-classical cadherin junctions, and accelerates the cell adhesion. The cis-clustering thus kinetically controls cell-adhesion before trans-binding. Notably, M2-macrophages predominantly express cadherin-23 and rapidly attach to circulatory tumor cells during metastatic migration. However, the relation of cis-clustering with rapid cell-cell adhesion in physiology is not yet established
Curcumin sensitizes prolactinoma to bromocriptine by activating the ERK/EGR1 and inhibiting AKT/GSK3β signaling pathway
Authors: Tang Chao , Zhu Junhao , Yuan Feng , Yang Jin , Cai Xiangming , Ma Chiyuan 
Published: June 2021

Abstract
Background

Although bromocriptine (BRC) as first-line drugs are recommended for treating patients with prolactinoma, a minority of patients with prolactinoma resistance to BRC. Curcumin (Cur) has been shown to inhibit proliferation of prolactinoma cell lines. The aim of this study is to investigate whether Cur could enhance the growth-inhibitory effect of BRC resistance on prolactinoma cell lines and its possible mechanism.
Methods

CCK-8 kit was used to test cell growth. Cell-cycle analysis and apoptosis was performed by flow cytometry. Electron microscopy was used to test autophagosome. The mRNA expression profiles were analysed using the Affymetrix Gene-Chip array. Western blotting was used to test protein expression. The SPSS version 17.0 software was applied for statistical analysis.
Results

Our data showed that Cur enhanced the growth-inhibitory effect of BRC on GH3 and MMQ cell proliferation. BRC and Cur both induced cell apoptosis, and Cur could significantly increase the apoptosis of BRC on pituitary adenoma cells through the ERK/EGR1 signaling pathway. Moreover, Cur could enhance the autophagic cell death (ACD) of BRC on tumor cell by inhibiting the AKT/GSK3β signaling pathway. The same results were confirmed in vivo study.
Conclusion

Cur sensitizes rat pituitary adenoma cell to BRC by activating the ERK/EGR1 and inhibiting AKT/GSK3β signaling pathway.