bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of Cytochrome P450 (CYP) 2C8 Polymorphisms on the Efficacy and Tolerability of Artesunate-Amodiaquine Treatment of Uncomplicated Plasmodium Falciparum Malaria in Zanzibar
Authors: Pernaute-Lau Leyre , Morris Ulrika , Msellem Mwinyi , Mårtensson Andreas , Björkman Anders , Gil Jose Pedro 
Published: November 2020

Abstract
Background The antimalarial drug amodiaquine, a commonly used long acting partner drug in artemisinin-based combination therapy, is metabolized to active desethyl-amodiaquine (DEAQ) by cytochrome P450 2C8 (CYP2C8). The CYP2C8 gene carries several polymorphisms including the more frequent minor alleles CYP2C8*2 and CYP2C8*3. These minor alleles have been associated with decreased enzymatic activity, slowing the amodiaquine biotransformation towards DEAQ. This study aimed to assess the influence of CYP2C8 polymorphisms on the efficacy and tolerability of artesunate-amodiaquine treatment for uncomplicated Plasmodium falciparum malaria in Zanzibar.Methods We analysed data from 618 children <5 years with uncomplicated P. falciparum malaria enrolled in two randomized clinical trials comparing artesunate-amodiaquine and artemether-lumefantrine in 2002-2005 in Zanzibar. CYP2C8*2 and CYP2C8*3 genotypes were determined by PCR-restriction fragment length polymorphism and assessed in relation to clinical data on treatment outcome and tolerance. Results The allele frequencies of CYP2C8*2 and CYP2C8*3 were 17.5% (95% CI 15.4-19.7%) and 2.7% (95% CI 1.8-3.7%), respectively. There was no significant difference in the proportion of subjects carrying either CYP2C8*2 or CYP2C8*3 alleles amongst those with reinfections (44.1 %; 95% CI 33.8-54.8) or those with recrudescent infections (48.3%; 95% CI 29.4-67.5), compared to those with adequate clinical and parasitological response (36.7 %; 95% CI 30.0-43.9) (P = 0.25 and P = 0.31, respectively). However, patients carrying either the CYP2C8*2 or CYP2C8*3 allele were significantly associated with increased occurrence of non-serious adverse events compare with CYP2C8 *1/*1 wildtype homozygotes (44.9%; 95% CI 36.1-54.0 versus 28.1%; 95% CI 21.9-35.0, respectively; P = 0.003). Conclusions CYP2C8 genotypes did not influence treatment efficacy directly, but the tolerability to ASAQ may be reduced in subjects carrying the CYP2C8*3 and CYP2C8*2 alleles. The importance of this non-negligible association with regards to amodiaquine-based malaria chemotherapy warrants further investigation.
A framework for the implementation of certification procedures at nurse level: a case study in a French hospital
Authors: SALMA Israa , WAELLI Mathias 
Published: November 2020

Abstract
Background

The implementation of certification procedures across healthcare systems is an essential component of the management process. In the past, several promising approaches have been developed towards the successful implementation of such policies, however, precise adaptation and implementation at the local context is essential. Thus, local activities must be considered to generate more pragmatic recommendations for managers. In this pilot study, we built an implementation framework for the inception of certification in healthcare facilities, particularly at nurse level activities. Our hypothesis comprised two objectives: the identification of key implementation process components, and the precise definition of these elements within local social activities.
Methods

This study used a two-step abductive approach. The first was inductive, and consisted of a qualitative case study, where we analysed the implementation of certification procedures in a French teaching hospital. The study was conducted between April and December 2019. Data were collected using semi-structured interviews, and observations by shadowing. In the second step, the emerging data were analysed using two approaches: The Quality Implementation Tool (QIT) and Translational Mobilisation Theory (TMT).
Results

Sixteen interviews were conducted with managers and nurses. We also accumulated 83 observational hours from two different wards. Our results showed that, first, all the retrieved elements over the implementation of certification procedures were captured by the QIT components and only one component was no applicable for the studied case. Second, we identified the elements in the local context of activity, with the different interrelationships between actors, actions and contexts, through the TMT. Third, our analyses were integrated and translated into a framework that described the implementation of certification procedures in healthcare facilities and with interest to the implementation at nurse/mid-managers level. In adopting QIT, the framework components took a transversal aspect then adapted to the local context of work through the TMT.
Conclusions

In this study, we generated an implementation framework that underpinned a certification procedures implementation. Our approach revealed broad interactions between proximity managers, teams and contexts during change mobilisation, not captured by transversal framework only as QIT. Going forward, this framework must be tested in future empirical studies.
Heat-Killed Malassezia Pachydermatis Suspension Modulates the Activity of Macrophages Challenged with Encephalitozoon Cuniculi
Authors: Codeceira Jéssica Feliciana , Alvares-Saraiva Anuska Marcelino , Hurtado Elizabeth Cristina Perez , Spadacci-Morena Diva Denelle , Coutinho Selene Dall´Acqua , Lallo Maria Anete 
Published: November 2020

Abstract
Background Encephalitozoon cuniculi, are obligate intracellular fungi that determine emerging diseases in humans and other animals, with economic relevance. Studies have shown that Malassezia are able to modulate the production of pro and anti-inflammatory cytokines by keratinocytes and human monocytes and has an immunomodulatory effect. In the present work, we evaluate the effects of heat-killed M. pachydermatis suspension on the modulation of the response of macrophages challenged with the microsporidia E. cuniculi. Methods Heat-killed M. pachydermatis suspension was used to treat macrophage for 1 hour, subsequently, macrophages were infected with spores of E. cuniculi (2:1) and evaluated at 15, 30, 60 minutes and 48 hours. To determine the phagocytic capacity (PC) and index (PI), cultures were stained with Calcofluor and the spores, internalized or not, were counted. Results Microbicidal and phagocytic activity was evaluated by transmission electron microscopy (TEM). The untreated macrophages and had PC, PI, and larger amounts of phagocytosed spores than those treated, but by TEM it was observed that in macrophages treated the microbicidal activity was faster, since in the phagocytic vacuoles there were few spores in different degrees of degeneration and few amounts of amorphous material. Macrophages treated with heat-killed M. pachydermatis suspension showed lower PI and PC, with the incipient presence of E. cuniculi in phagosomes inside these macrophages. Additionally, these same treated macrophages had a mixed pattern of cytokine release with a Th1, Th2 and Th17 profile, with emphasis on IL-10, IL-4, IL-17, IL-6 and IFN-g secretion, particularly greater production of anti-inflammatory cytokines. Conclusions Our results showed that the treatment with heat-killed M. pachydermatis suspension determined an increase in the release of cytokines and reduced the phagocytic activity of macrophages challenged with E. cuniculi
Exclusive Breastfeeding Duration Modified the Effects of Neonatal and Familiar Risk Factors on Childhood Asthma and Allergy: A Population-Based Study
Authors: Hu Yabin , Chen Yiting , Liu Shijian , Jiang Fan , Wu Meiqin , Yan Chonghuai , Tan Jianguo , Yu Guangjun , Hu Yi , Yin Yong , Qu Jiajie , Li Shenghui , Tong Shilu 
Published: November 2020

Abstract
Background: Childhood asthma and allergic diseases are a significant global problem. There are inconsistent findings on the associations of delivery mode, the number of children in the household and breastfeeding with childhood asthma and allergic diseases. We assessed these associations and examined whether breastfeeding modified the effects of neonatal and familiar risk factors on childhood asthma and allergic diseases.Methods: A population-based cross-sectional study was conducted in Shanghai, China. A total of 17 primary schools were randomly selected from 13 districts of Shanghai in this study. The International Study of Asthma and Allergies in Childhood questionnaire was adopted to assess the childhood asthma and allergic diseases. Multivariable logistic regression models were used to evaluate the associations between neonatal and familiar factors and childhood asthma and allergic diseases, and to examine the modification effects of breastfeeding on the associations assessed.Results: Of 10,464 primary school children aged 6-11 years, the overall prevalence of childhood asthma, allergic rhinitis, urticarial, food allergy and drug allergy was 13.9%, 22.7%, 15.3%, 8.1% and 4.6%, respectively. Male sex, high socioeconomic status, cesarean section delivery, only one child in the household and having family history of allergy were among the major risk factors for childhood asthma and allergic diseases while longer exclusive breastfeeding duration (＞6 months) was a protective factor. Longer exclusive breastfeeding duration also attenuated the effects of neonatal and familiar risk factors on childhood asthma and allergic diseases. Conclusions: Longer exclusive breastfeeding duration was a protective factor against childhood asthma and allergic diseases, and also reduced the adverse effects of neonatal and familiar risk factors on these diseases. Giving the prevalence of childhood asthma and allergic diseases is rapidly rising across the globe, these findings may have important clinical and public health implications.
EFNA3&nbsp;Can Serve as Potential Prognostic Biomarker for Luad Patients: A Comprehensive Analysis of the Eph/Ephrin&nbsp; Family
Authors: Hou Gang , Deng Mingming , Tong Run , Zhang Zhe , Wang Tao , Liang Chaonan , Zhou Xiaoming 
Published: November 2020

Abstract
Background: Ephrin receptors (Eph) and their ligands called ephrins, function in various disease processes. However, the specific mechanism of Eph/ephrins in lung adenocarcinoma (LUAD) are still unclear.Methods: Oncomine and GEPIA databases were used to explore the differential expression of Eph/ephrins in LUAD. The Kaplan–Meier plotter was selected to explore the prognostic value of Eph/ephrins. The cBioPortal database was used to analyze the genetic variation of the EFNA3 gene. Clinical LUAD tissue was analyzed by immunohistochemistry identifying the clinical value of identifying the ephrin-A3 protein. Weighted Co-expression Network Analysis (WGCNA) and Gene set enrichment analysis (GSEA) identified the potential regulatory mechanism of EFNA3.Results: EPHA10, EFNA3/4/5 and EPHB1/2 mRNA expression levels were significantly increased in LUAD. EFNB1/2 and EPHB6 expression levels were significantly decreased. Prognostic analysis showed that EFNA3, EFNB1/2, and EPHB2 expression were significant correlate with both overall survival (OS) and progression-free survival (PFS) in LUAD patients. Next, the expression of the EFNA3 protein was increased in LUAD tissues and was designated as an independent risk prognosis factor. Mechanistically, EFNA3 may be involved in nuclear division, synaptic function, and ion channel activity-related pathways. Additionally, higher expression of EFNA3 was significantly correlated with OS in pan-cancer patients.Conclusions: This study revealed the abnormal expression and prognostic value of Eph/Ephrin family members in LUAD. In addition, it is emphasized that EFNA3 may be a novel biomarker for the diagnosis and prognosis of LUAD patients.
Adhatoda Vasica: A Potential Ayurvedic Intervention Against COVID-19 Associated Impaired Immune Response and Hypoxia-Inflammation Phenotype
Authors: Gheware Atish Prabhakar , Dholakia Dhwani , Kanan S , Panda Lipsa , Anand Vivek , Rani Ritu , Pattnaik Bijay Ranjan , Jain Vaibhav , Subramanian V , Mukerji Mitali , Agrawal Anurag , Prasher Bhavana 
Published: November 2020

Abstract
Background: The importance of hypoxia inducible factor-1 α (HIF-1α) stabilization in uncontrolled infection and inflammation is widely accepted. Several inhibitors of HIF signalling are in clinical trials for malignancy, ischemia and inflammatory diseases. Increased hypoxia is being reported to be an important modifier for several pathological features of COVID-19 such as impaired immunity, hyper-inflammation, thrombosis, lung injury and sepsis. Methods: In this study we tested the effect of whole aqueous extract Adhatoda Vasica (AV), that our group has shown to have anti-hypoxic and anti-inflammatory effects, on various outcomes of hypoxic response. Effects of AV were assessed in preclinical mouse models of pulmonary fibrosis, bacterial sepsis and siRNA induced hypoxia-thrombosis phenotype. Therapeutic relevance of AV in current pandemic were also examined through transcriptome and molecular docking analysis. Results: Oral administration AV extract attenuated the increased levels of airway inflammation, collagen content, transforming growth factor-b1 (TGF-b1), IL-6, HIF-1α and improved the overall survival rate in bleomycin treated and Cecum Ligation and Puncture (CLP) induced mice. AV treatment also rescued the prolyl hydroxylase domain 2 (phd2) siRNA induced HIF-1α and associated blood coagulation phenotypes in mice. Transcriptome analysis of lungs of AV treated naïve mice reveal downregulation of hypoxia, inflammation, TGF-b1 and angiogenesis and upregulation of adaptive immunity related genes. These genes and pathways show opposite expression in transcriptome of BALF and PBMCs of SARS-CoV2 infected patient. Molecular docking of AV constituents presents in extract reveal many molecules with low binding energy (≤ -8) to multiple SARS-CoV2 and host target proteins that are relevant in viral entry and replication. Conclusion: Our results provide a scientific rationale for this ayurvedic herbal medicine in ameliorating the hypoxia-hyperinflammation features which could be useful against SARS-CoV-2 infection.
Differentially expressed liver exosome-related genes as a candidate prognostic biomarker for hepatocellular carcinoma
Authors: Zuo Bangyou , Zhao Haitao , Bian Jin , Long Junyun , Yang Xu , Hu Bo , Yang Xiaobo , Sang Xinting 
Published: November 2020

Abstract
Background

The function of exosome includes cell-to-cell communication, neovascularization, and metastasis of cancer cell and drug resistance, which plays an important part in the occurrence and progression of hepatocellular carcinoma (HCC). Because the mechanism in this area is less studied, our goal is to identify exosome-related genes in HCC, establish a reliable prognostic model for liver cancer patients, and explore its underlying mechanisms.
Methods

The exoRbase database and The Cancer Genome Atlas (TCGA) database were used to analyze differentially expressed genes (DEGs). Cox regression and LASSO analysis were applied to determine DEGs closely related to overall survival (OS). Then the exosome-related prognostic model was constructed in TCGA and validated in the database of International Cancer Genome Consortium (ICGC). Nomogram graph was performed to predict the survival. CIBERSORT was used to estimate the score of different type of immune cells. DEGs related to immunotherapy are used to predict the effect of immunotherapy.
Results

48 exosome-related DEGs were obtained and five genes (XPO1, IFI30, FBXO16, CALM1, MORC3) among them were selected to construct predictive model. Then we divided the HCC patients into low-risk and high-risk groups by the best cut-off value according to the X-tile software. The high-risk related to exosome were significantly associated with a poor prognosis. Moreover, the features related to exosome could positively regulate immune response. At the same time, the proportion of T cell regulatory factors (Tregs) and macrophages M2 is higher in the high-risk group, and high-risk group exhibited higher expression of immune checkpoint molecular including PD-L1, PD-L2, TIGIT, and IDO1.
Conclusions

Overall, our research showed that markers related to exosomes were potential biomarkers for the prognosis of HCC, providing an immunological perspective for the development of precision treatment.
Construction and Validation of a Ferroptosis-Related Prognostic Signature in Kidney Renal Clear Cell Carcinoma
Authors: Sun Zhuolun , Jing Changying , Xiao Chutian , Zhang Mingxiao , Wang Zhenqing , Li Mingzhao , Wang Hua 
Published: November 2020

Abstract
Background: Kidney renal clear cell carcinoma (KIRC) is the most common and lethal renal cell carcinoma (RCC) histological subtype. Ferroptosis is a newly discovered programmed cell death and serves an essential role in tumor occurrence and development. The purpose of this study is to analyze ferroptosis-related gene (FRG) expression profiles and to construct a multi-gene signature for predicting the prognosis of KIRC patients.Methods:RNA-sequencing data and clinicopathological data of KIRC patients were downloaded from The Cancer Genome Atlas (TCGA). Differentially expressed FRGs between KIRC and normal tissues were identified using ‘limma’ package in R. GO and KEGG enrichment analyses were conducted to elucidate the biological functions and pathways of differentially expressed FRGs. Consensus clustering was used to investigate the relationship between the expression of FRGs and clinical phenotypes. Univariate and the least absolute shrinkage and selection operator (LASSO) Cox regression analysis were used to screen genes related to prognosis and construct the optimal signature. Then, a nomogram was established to predict individual survival probability by combining clinical features and prognostic signature.Results: A total of 19 differentially expressed FRGs were identified. Consensus clustering identified two clusters of KIRC patients with distinguished prognostic. Functional analysis revealed that metabolism-related pathways were enriched, especially lipid metabolism. A 7-gene ferroptosis-related prognostic signature was constructed to stratify the TCGA training cohort into high- and low-risk groups where the prognosis was significantly worse in the high-risk group. The signature was identified as an independent prognostic indicator for KIRC. These findings were validated in the testing cohort, the entire cohort, and the International Cancer Genome Consortium (ICGC) cohort. We further demonstrated that the signature-based risk score was highly associated with the KIRC progression. Further stratified survival analysis showed that the high-risk group had a significantly lower overall survival (OS) rate than those in the low-risk group. Moreover, we constructed a nomogram that had a strong ability to forecast the OS of the KIRC patients.Conclusion: We constructed a ferroptosis-related prognostic signature, which might provide a reliable prognosis assessment tool for clinician to guide clinical decision-making and outcomes research.
Identification of SHMT2&nbsp;as a Potential Prognostic Biomarker and Correlating With Immune Infiltrates in Lung Adenocarcinoma
Authors: Luo Lianxiang , Zheng Yushi , Lin Zhiping , Li Xiaodi , Li Xiaoling , Li Mingyue , Cui Liao , Luo Hui 
Published: November 2020

Abstract
Background: The role of Serine hydroxymethyltransferase2 (SHMT2) in diverse cancers has attracted increasing attention. However, the prognostic role of SHMT2 in lung adenocarcinoma (LUAD) and its relationship with immune cell infiltration is yet to be studied.Methods: The data of mRNA and clinic in LUAD were respectively downloaded from the GEO and TCGA database. We conducted a biological analysis to select the signature gene SHMT2. Online databases including Oncomine, GEPIA, TISIDB, TIMER, and HPA were applied to analyze the characterization of SHMT2 expression, prognosis and the correlation with immune infiltrates in LUAD.Results: The mRNA expression and protein expression of SHMT2 in LUAD were higher than normal tissue. A Kaplan-Meier analysis showed the lower expression level of SHMT2 had a better overall survival rate. Multivariate analysis and the Cox proportional hazard regression model revealed that SHMT2 expression was an independent prognostic factor for patients with LUAD. Meanwhile, the gene SHMT2 was highly associated with tumor-infiltrating lymphocytes in LUAD.Conclusions: These results suggest that the SHMT2 gene is a promising candidate as a potential prognostic biomarker and highly associated with different types of phenotypes of immune cell infiltration in LUAD.
Noise Modeling to Build Training Sets for Robust Speech Enhancement
Authors: Wang Yahui , Zhang Wenxi , Wang Yongbiao , Kong Xinxin , Zhang Hongxin 
Published: November 2020

Abstract
The performance of Deep Neural Network (DNN)-based speech enhancement models degrades significantly in real recordings because the synthetic training sets are mismatched with real test sets. To solve this problem, we propose a new Generative Adversarial Network framework for Noise Modeling (NM-GAN) that can build training sets by imitating real noise distribution. The framework combines a novel U-Net with two bidirectional Long Short-Term Memory (LSTM) layers that act as a generator to construct complex noise. The Gaussian distribution is adapted and used as conditional information to direct the noise generation. A discriminator then learns to determine whether a noise sample is from the model distribution or from a real noise distribution. By adversarial and alternate training, NM-GAN can generate enough recall (diversity) and precision (quality of noise) in its samples for it to look like real noise. Afterwards, realistic-looking paired training sets are composed. Extensive experiments were carried out and qualitative and quantitative evaluation of the generated noise samples and training sets demonstrate that potential of the framework. An Speech enhancement model trained on our synthetic training sets and on real training sets was found to be capable of good noise suppression for real speech-related noise.