bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metagenomic survey of agricultural water using long read sequencing: considerations for a successful analysis
Authors: Maguire Meghan , Kase Julie A. , Brown Eric W. , Allard Marc , Musser Steve , González-Escalona Narjol 
Published: September 2021

Abstract
Background

Leafy greens are responsible for nearly half of the produce-related Shiga toxin-producing Escherichia coli (STEC) outbreaks in the United States and recent investigations have implicated agricultural water as a potential source. Current FDA detection protocols require extensive analysis time. Development of methods for rapid detection of STECs in the field are imperative to maintain food safety. We aimed to use Oxford Nanopore rapid sequencing kits for an in-field determination of agricultural water microbiome and possible detection and characterization of STECs strain(s) in these samples.
Results

We tested the performance of the nanopore rapid sequencing kit (RAD004) for fast microbiome determination using the well characterized ZymoBIOMICS mock microbial community and the number of reads for each identified species was present in the expected proportion. Rapid sequencing kit (LRK001 and RAD004) library preparation of DNA extracted from agricultural water resulted in poor nanopore sequencing reactions, with low output (0.3–1.7 M reads), a high proportion of failed reads (50–60%), and highly sheared DNA before and after a magnetic bead clean up. To improve performance, we prepared a DNA library with the ligation kit (LSK109), which includes multiple cleaning steps, reducing inherent inhibitors and producing a better outcome (2.2 M reads, 15% failed reads). Metagenomic composition of four sample sites determined using the ligation kit, showed a highly diverse bacterial community for each site, with 11 total genera identified, including Synechococcus and Cyanobium. No definitive presence of STEC could be confirmed in any of the sites. Approximately 100 reads from each site (0.02% of total reads) were identified as Escherichia coli, but the specific strain or their virulence genes could not be detected. Sites 9, 10, and 12 were found to be positive for STEC presence by microbiological techniques after enrichment.
Conclusions

The rapid sequencing kits can be appropriate for genus or species level microbial identification, but we recommend the use of the ligation kit for increased sequencing depth and removal of contaminants in agricultural water. However, we were not able to identify any STEC strains in these nanopore microbiome samples, due to low initial concentrations. The results from this pilot study provide preliminary evidence that MinION sequencing of agricultural water using the ligation kit has the potential to be used for rapid microbiome determination in the field with optimal results for water quality surveillance.
Publication Landscape on Cushing's Disease: From the Past 40 Years to Future Directions
Authors: Luo Ming-Jie , Du Kelei , Guo Xiaopeng , Wang Zihao , Xing Bing 
Published: September 2021

Abstract
PurposeThough literature related to Cushing's disease (CD) has grown significantly, previous reviews exclusively focused on specific research areas and were biased towards highly cited articles. This study aims to systemically analyze the research landscapes and trends using unbiased methods. MethodsWe queried all the CD-related publications in PubMed and clinical trials registered on clinicaltrials.gov. Latent Dirichlet allocation (LDA), a machine learning method, was used to derive research hotspots from article texts. The research topic clusters and country-level collaboration were revealed by network analysis.Results5015 articles were published since 1981, currently growing at 155 per year, with more retrospective studies but fewer prospective studies. Interestingly, the most popular LDA research topics were complications and comorbidities, endocrine hormone tests and surgical therapy, and they formed a remarkable triangle relationship in the research topic network. These topics had numerous international studies and were supported by most funding. In addition, many topics in the basic research domain were proliferating, including mutation, biomarkers, endopeptidases, and other molecular genetics and pathology of CD. Out of 63 registered clinical trials, over 25% were withdrawn due to inadequate patient recruitment or lack of funding.ConclusionsThis publication landscape analysis provided a systemic representation of CD literature regarding the history, current challenges, and future directions, enabling clinicians a rapid and comprehensive insight into the disease.
Patients’ Perspectives on User Involvement in General Practice. A Qualitative Analysis of Free-Text Comments
Authors: Nørgaard Birgitte , Titlestad Signe Beck , Marcussen Michael 
Published: September 2021

Abstract
Background: General practice plays a core role in managing the pathways of patients with chronic diseases. Despite the increased focus on patient involvement in healthcare practice and well-established knowledge of the benefits of involvement and personalized care, involvement in general practice appears to be challenged. This study aimed to explore patient involvement in general practice from the patients’ perspectives. Method: The study involved a questionnaire survey investigating patient involvement in general practice from the patients’ perspectives. The validated questionnaire includes an open-ended question encouraging responders to provide additional comments regarding their involvement in general practice. The results from these comments are presented in this paper. A thematic analysis was applied. Results: Of the 468 responses, 139 included additional comments to the free-text question. Through our analysis, six analytic themes were generated—To be seen, met, or heard, To feel safe or not, To be involved or dictated to, Accessibility, COVID-19, and For the resourceful—across 116 codings and 25 descriptive themes. The themes’ interwovenness underscores the complexity of both involvement and how it is to live with a chronic disease. Our analysis indicates that involvement in general practice is for the resourceful.Conclusion: The six themes describing involvement in general practice from the perspectives of patients with T2DM and/or COPD were deeply intertwined. Involvement is dependent on being seen, met, and heard, all of which contribute to the patients’ sense of feeling safe (or not). These aspects are dependent on accessibility to a general practitioner; thus, COVID-19 was a barrier during the data-collection period. Furthermore, it appeared that being resourceful not only contributed to a sense of being involved in general practice but was perhaps even a prerequisite for being involved.
From Each According to Means, to Each According to Needs? Distributional Effects of Abolishing Asset-Based Payments for Residential Care in Austria
Authors: Rodrigues Ricardo , Simmons Cassandra , Premrov Tamara , Böhler Christian , Leichsenring Kai 
Published: September 2021

Abstract
BackgroundMost countries in Europe require out-of-pocket payments (OPPs) for nursing homes based on users’ income and often assets. This was also the case in Austria until 2018 when asset-based contributions to residential care —denoted the ‘Pflegeregress’ – were abolished, leaving a shortfall in revenue. We aim to determine how the Pflegeregress was distributed across different groups in Austria prior to 2018, what the distributional consequences of its abolishment were, and what the distributional impact of different financing alternatives would be.MethodsCircumventing data availability issues, we construct a micro-simulation model using a matched administrative dataset on residential care users receiving the Austrian care allowance (Pflegegeldinformation, PFIF, HVB, and Pflegedienstleistungsstatistik, Statistik Austria) and survey data (SHARE, wave 6). Using this model, we estimate the expected duration of residential care and OPPs under the Pflegeregress of a representative sample of older people aged 65+ in Austria, as well as OPPs under budgetary neutral financing alternatives to the abolished asset-based contribution, namely an inheritance tax and a social insurance scheme. The distributional impact of abolishing the Pflegeregress and these alternative scenarios is assessed through a number of measures, such as ability to pay, Concentration Indices (CI) and a needs-standardized measure.ResultsWe find that lower income individuals and homeowners disproportionately contributed to asset-based OPPs for residential care prior to 2018 due in large part to their higher use of residential care and the low asset-exemption thresholds. These groups were therefore the largest beneficiaries of its abolishment. The alternative financing scenarios tested would result in a more progressive distribution of payments (i.e. concentrated on more affluent individuals). ConclusionOur findings indicate the limited ability of asset-based OPPs to target those with higher assets, thus questioning the fairness of these instruments for financing residential care facilities for older people in Austria. Findings also suggest that the parameterization of such OPPs (such as asset exemption thresholds) and patterns of residential care use are key variables for assessing the distribution of asset-based OPPs for residential care use. Policy alternatives that decouple payments from use would entail greater transfers from healthy to less healthier individuals.
Targeting miR-9 in Glioma Stem Cell-Derived Extracellular Vesicles: A Novel Diagnostic and Therapeutic Biomarker
Authors: Geng Liangyuan , Xu Jinjin , Zhu Yihao , Hu Xinhua , Liu Yong , Yang Kun , Xiao Hong , Zou Yuanjie , Liu Hongyi , Ji Jing , Liu Ning 
Published: September 2021

Abstract
Background Glioblastoma, the lethal brain tumor with undesirable prognosis, still has no effective strategies in early diagnosis and treatment. Extracellular vesicles (EVs) isolated from cerebrospinal fluid (CSF) are a potential liquid biopsy source. This study was performed to assess the miRNA expression profiles in EVs from CSF and tissue of GBM patients to identify significantly upregulated miRNAs and investigate the underlying neoplastic mechanisms.Methods EVs were measured by TEM and NTA assays. Differentially regulated miRNAs were measured using RNA sequencing in GBM CSF EVs and in GBM tissues compared with controls. RT-qPCR was employed to analyze certain miRNA and gene expression. Luciferase report assay was used in investigate downstream gene target of miR-9. The proliferation ability was detected by EdU and CCK-8 experiment while cell migration was measured by transwell and wound healing assay.Results The expression level of miR-9 was significantly higher in GBM CSF EVs and tissues than controls (p = 0.038). The area under curve for CSF EV miR-9 was 0.080 (95% CI: 0.583–1.000, p = 0.033). The expression of miR-9 was significantly higher in GSCs and GSC-derived EVs compared with glioblastoma cells. GSC culture medium, which contained the GSC-derives EVs, could promote GBM growth and migration after administration to GBM cells. Moreover, inhibition of miR-9 in GSCs showed the reverse anti-tumor effects. MiR-9 could bind to the 3’UTR region of DACT3 and suppress its expression. The miR-9/DACT3 axis might attribute to GBM malignant phenotype.Conclusion MiR-9 in CSF EVs might act as a novel diagnostic biomarker for GBM and targeting miR-9 by GSC-derived EVs may be a specific and efficient strategy for GBM biotherapy.
Edaravone Ameliorates Depressive and Anxiety-like Behaviors via Sirt1/Nrf2/HO-1/Gpx4 Pathway
Authors: Dang Ruozhi , Wang Mingyang , Li Xinhui , Wang Haiyang , Liu Lanxiang , Wu Qingyuan , Zhao Jianting , Ji Ping , Zhong Lianmei , Licinio Julio , Xie Peng 
Published: September 2021

Abstract
Background: The inflammation and oxidative stress (OS) have been considered crucial components of the pathogenesis of depression. Edaravone (EDA), a free radical scavenger, processes strong biological activities including antioxidant, anti-inflammatory and neuroprotective properties. However, its role and potential molecular mechanisms in depression remain unclear. The present study aimed to investigate the antidepressant activity of EDA and its underlying mechanisms.Methods: A chronic social defeat stress (CSDS) depression model was performed to explore whether EDA could produce antidepressant effects. C57BL/6J mice were intraperitoneally injected with EDA or Vehicle daily for 10 days. Behaviors tests were then carried out to examine depressive, anxiety-like and cognitive behaviors including social interaction (SI) test, sucrose preference test (SPT), open field test (OFT), elevated plus maze (EPM), novel object recognition (NOR), tail suspension test (TST) and forced swim test (FST). Hippocampal and medial prefrontal cortex (mPFC) tissues were collected for Nissl staining, immunofluorescence, targeted energy metabolomics analysis, measurement of MDA, SOD, GSH and transmission electron microscopy (TEM). Western blotting (WB) and quantitative real time polymerase chain reaction (qRT-PCR) detected the Sirt1/Nrf2/HO-1/Gpx4 signaling pathway. Knockdown experiments were performed to determine the effects of Gpx4 on CSDS mice with EDA treatment by an adeno-associated virus (AAV) vector containing miRNAi(GPX4)-EGFP infusion.Results: The administrated of EDA dramatically ameliorated CSDS-induced depressive and anxiety-like behaviors. Additionally, EDA notably attenuated neuronal loss, microglial activation, astrocyte dysfunction, oxidative stress damage and energy metabolism in the hippocampus (Hip) and mPFC of CSDS-induced mice. Further examination indicated that the application of EDA after the CSDS model significantly increased the protein expressions of Sirt1, Nrf2, HO-1 and Gpx4 in the Hip. In addition, Gpx4 knockdown in CSDS mice abolished EDA-generated efficacy on depressive and anxiety-like behaviors.Conclusion: These findings suggest that EDA possesses potent antidepressant and anxiolytic properties through Sirt1/Nrf2/HO-1/Gpx4 axis and Gpx4-mediated ferroptosis may play a key role in this effect.
Sleep and Alzheimer’s Disease: Shared Genetic Risk Factors, Drug Targets, Molecular Mechanisms, and Causal Effects
Authors: Chen Dongze , Wang Xinpei , Jia Jinzhu , Huang Tao 
Published: September 2021

Abstract
Background: Alzheimer’s disease (AD) was associated with sleep-related phenotypes (SRPs). Whether they share common genetic etiology remains largely unknown. We explored the shared genetics and causality between AD and SRPs by using high-definition likelihood (HDL), cross phenotype association study (CPASSOC), transcriptome wide association study (TWAS), and bidirectional Mendelian randomization (MR) in summary-level data for AD (n = 79145) and summary-level data for seven SRPs (sample size ranges from 345552 to 386577). Results: AD shared strong genetic basis with insomnia (rg = 0.20; P = 9.70×10-5), snoring (rg = 0.13; P = 2.45×10-3), and sleep duration (rg = -0.11; P = 1.18×10-3). CPASSOC identifies 31 independent loci shared between AD and SRPs, including four novel shared loci. Functional analysis and TWAS showed shared genes were enriched in liver, brain, breast, and heart tissues, and highlighted the regulatory role of immunological disorders, very-low-density lipoprotein particle clearance, triglyceride-rich lipoprotein particle clearance, chylomicron remnant clearance and positive regulation of T cell mediated cytotoxicity pathways. Protein-protein interaction analysis provided three potential drug target genes (APOE, MARK4 and HLA-DRA) that interacted with known FDA-approved drug target genes. CPASSOC and TWAS demonstrated three regions 11p11.2, 6p22.3 and 16p11.2 may account for the shared basis between AD and sleep duration or snoring. MR showed AD had causal effect on sleep duration (βIVW = -0.056, PIVW = 1.03×10-3). Conclusion: Our findings provide strong evidence of shared genetics and causation between AD and sleep, and advance our understanding the genetic overlap between them. Identifying shared drug targets and molecular pathways can be beneficial to treat AD and sleep disorders more efficiently.
Comprehensive Analysis and Validation of Solute Carrier Family 25 (SLC25) in Pan-Cancer
Authors: Liu Ao-ran , Liu Ying-nan , Shen Shi-xuan , Yan Li-rong , Lv Zhi , Ding Han-xi , Wang Ang , Yuan Yuan , Xu Qian 
Published: September 2021

Abstract
BackgroundAs the largest gene family functioning in protein transport among human solute carriers, the SLC25 family (mitochondrial carrier family) has been reported to be associated with the genesis and development of many diseases. However, acomprehensiveexplorationfor the roles of SLC family in cancer remains lacking. MethodIn the present study, a total of 15 functional SLC25 family genes were retrieved from all current publications. And multi-dimensional analyses were systematically performed based on the transcriptome and genome data of SLC25 family from a variety of online databases for their expression, mutation and copy number variation, cancer prognosis, signaling pathways and immune cell infiltration. Validation by qPCR was further conducted for the expression of partial SLC25 family members in some tumor tissue.ResultsWe found that SLC25A7 was highly expressed in stomach adenocarcinoma, kidney chromophobeand colon adenocarcinoma, while low expressed in lung adenocarcinoma， thyroid carcinomaas well as head and neck squamous cell carcinoma. SLC25A23 was decreased in colon adenocarcinoma andhead and neck squamous cell carcinoma. SLC25A4 was down-regulated instomach adenocarcinoma,colon adenocarcinoma, kidney renal clear cell carcinoma and head and neck squamous cell carcinoma. Validation results of stomach adenocarcinoma and colon adenocarcinoma were consistent with our bioinformatic prediction. The analysis in regard to cancer-related pathways indicated that SLC25A5 was more likely to be positively associated with carcinogenic pathways such as PI3K-AKT-MTOR, MYC-TARGETS-V2 and E2F-TARGETS. Immune cells including Macrophages M2 and B cells naïve had significant association with SLC25s expression. Survival analysis demonstrated that SLC25A8 was linked to a high-risk effect on the prognosis of cervical squamous cell carcinoma and adenocarcinoma significantly. The majority of SLC25 genes showed high mutation frequency in uterine corpus endometrial carcinoma withan overall average mutation rateof 0.100189. SLC25A8 had extensive copy number variation in different cancer tissue. And SLC25A25 showed high mutation frequency in breast cancer cell lines. As forthe influence of mutation on gene expression and cancer prognosis, SLC25A4 mutation could alter its expression in uterine corpus endometrial carcinoma. Most SLC25 gene mutationmadeprominent effects on the prognosis of patients with uterine corpus endometrial carcinoma. ConclusionAll these findings suggested that the SLC25 family might be crucial to the occurrence, progression and prognosis of tumor. They had the potential to be predictive biomarkers for early diagnosis and prognosis as well as novel targets for individualized treatment of cancer.
Reduced Order Model-based Observer Design for Online Temperature Distribution Estimation in Lithium-ion Batteries
Authors: Fan Bi , Zhuang Yufen , Liu Zhen , Gan Min , Xu KangKang 
Published: September 2021

Abstract
Time/space separation-based modeling methods have been widely researched for estimating lithium-ion battery (LIB) thermal dynamics. However, these methods have been developed in an offline environment and may not perform well in real-time application since the battery systems in electric vehicles (EVs) are usually subject to external disturbances. Furthermore, the onboard measurements of temperature are often corrupted by significant error. To address these problems, we present a reduced model-based observer design for online temperature distribution estimation in LIBs. First, an extreme learning machine (ELM) based offline spatiotemporal model is constructed to approximate the thermal dynamics of LIB. Second, an adaptive reduced order observer is designed based on the offline model developed in the previous step. The offline model is then updated with the estimation results of the observer. As the performance of the estimator is highly related to the placement of sensors, a genetic algorithm (GA) based integrated optimization strategy is also developed to determine the optimal sensor location for online estimation. Finally, the whole temperature distribution is estimated in real time using the observer, the measured voltage, current and the limited available temperature data. Simulation results on a battery thermal system verify the effectiveness of this developed model.
Determinants of Infant and Young Child Feeding Practices in Lower Egypt: A Community- Based Cross-Sectional Survey
Authors: koofy Nehal El , Moawad Eman Mohamed Ibraheim , Tawfik Safaa , El-Sabakhawi Doaa Hamed Mohamed 
Published: September 2021

Abstract
Background: The optimal feeding practice in infants and young children is the key in shaping their adequate growth and development. Methods: The study aimed to explore the multiple interactions that influence the complexity of infant feeding in Egypt and acknowledge the common beliefs, attitudes and practices regarding breastfeeding and weaning process. Energy and nutrients daily intake provided by complementary foods was also investigated. Structured interview survey gathering data on maternal feeding practices related to infants and young children, clinical and nutritional status of infants and their nutrient daily intake was administered to 235 mother-infant pairs recruited from Nile Delta. Results: Exclusive breastfeeding was significantly reported in 55.8% (p < 0.001), being optimum in only 8.9 % of infants and significantly predicted in mothers aged 25-29 years. The complementary feeding started at ≥ 6 months in 58.3 % of infants and significantly based on commercial recipes ((p < 0.001). Cessation of breastfeeding (34.5 %) was mainly associated with maternal perception of insufficient breast milk (16.2 %) and significantly associated with female gender (p<0.001), rural residence (p<0.001), maternal age (25-29 years), parental occupation and paternal education (p<0.001). Calcium (58.7 %), vitamin B2 (45.1 %) and vitamin C (55.7 %) were the only nutrients adequately consumed. Conclusions: In Egypt, infant and young feeding practices are still far from the recommended levels. Collaboration between government entities and non-profit organizations is required to improve maternal knowledge, beliefs, attitudes and practices.