bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperaccumulation of lead using Agrostis tenuis
Authors: Anguilano Lorna , Onwukwe Uchechukwu , Dekhli Aghis , Venditti Susanna , Aryani Danny , Reynolds Alan 
Published: April 2022

Abstract
In recent years the quest for a circular economy approach and the upcycling of secondary raw materials have been pushed in the global political agenda. Increased interest has been taken by the recovery of materials from sludges, brines, contaminated waters and other media, such as “mining” of waste. Contaminated soils have an interesting role in this process, and various methodologies have been developed using chemical, bacteriological and pyrometallurgical cleaning procedures. However, these procedures all involve the movement of high volume of materials and the disruption of the industrial landscape; furthermore, they often require the use of hazardous solvents and high energy processes. This work proposes to identify less impactful methods aimed at the recovery of metals from mining areas while preserving the landscape and avoiding environmental impacts such as the increase of CO2 for transport and increase hazard through use of solvents, this takes particular importance in areas of industrial heritage status. In particular, this work focuses on the use of Agrostis tenuis, an autochthonous species in mining areas of the UK, as a “mining tool” for the removal of lead. The selection of both the hyperaccumulator and the metal in this study are derived from the evaluation of the most common contamination in mining areas and the widespread prevalence of this hyperaccumulator and its resilience in highly contaminated abandoned mines. Aside from its presence within the mining areas, making it an autochthonous plant, Agrostis tenuis is selected for its visual morphology. Being a short grass, Agrostis does not change the visual appearance of the mining sites, most of which in the UK have a historic landscape status.
Identification of key molecules for castration resistance prostate cancer by bioinformatic analysis
Authors: Hu Jieping , Yu Yue , Liu Wei , Xi Haibo 
Published: April 2022

Abstract
Objectives
Castration resistance prostate cancer (CRPC) is a complex tumor associated with highly mortality. To discover key molecular in CRPC, we dissected the data of CRPC based on arrays by bioinformatic analysis.
Methods
The gene expression profiling datasets of prostate cancer were analyzed online. The Database for Annotation, Visualization and Integrated Discovery (DAVID, https://david.ncifcrf.gov/) was used to perform Gene Ontology (GO) functional and KEGG pathway enrichment analyses. Molecular Complex Detection (MCODE) in Cytoscape software (Cytoscape_v3.6.1) was applied to screen hub genes. Gene expression data were obtained from ONCOMINE website (https://www.oncomine.org/). The gene expression and survival data were download and analyzed.
Results
4 datasets (GSE104935, GSE120005, GSE78201, and GSE21887) were included for analysis. The 15 overlap up regulated genes and 27 overlap down regulated genes were identified and analyzed by DAVID. 11 proteins corresponding to genes (ELOVL6, ABCA1, FOXO3, and TNRC6B; ALDH1A3, OSBPL8, ACSL3, SLC45A3, KLK2, FKBP5, and PMEPA1) were identified to be key genes. Gene expression suggested OSBPL8, PMEPA1 and SLC45A3 were different expressed in CRPC patients, these genes were also associated with survival.
Conclusions
OSBPL8, PMEPA1 and SLC45A3 were involved with CRPC. Their functions needed more detailed research to reveal.
Positive Selection Drives the Rapid Fixation of Dephosphorylation in IRF9
Authors: Chen Jianhai , He Xuefei , Jakovlić Ivan 
Published: April 2022

Abstract
The arms race between humans and pathogens drives the evolution of the human genome. Here, based on the HPO (Human Phenotype Ontology) annotation, we focused on human genes related to recurrent infections of virus, (RVI), bacterial (RBI) and recurrent fungal infections (RFI) to understand positive selection on pathogen-responsive genes. Interestingly, cross-species positive selection analyses revealed that the proportion of unique genes under positive selection was higher for RVI (78.57%) than for RFI (57.14%) and RBI (58.68%). Based on results of the branch-site test, we further focused on the amino acid site Val129 of IRF9, which has a significant signal of positive selection based on multiple evidence. Interestingly, this novel and derived amino acid (V) has been rapidly fixed before the "out-of-Africa" event ~ 500,000 years ago from the ancestral state S, which is conserved among 88.5% of mammalian lineages. Phosphorylation analysis revealed that the conserved ancestral S may serve as the phosphorylation site of IRF9. Further analyses suggested that the rapid dephosphorylation of IRF9 via the change of S to V may have conferred potential molecular adaptations by boosting and extending the immune activity of IRF9. This study provides an interesting mode in which strong positive Darwinian selection drives the rapid fixation of a hominin specific amino acid leading to molecular adaptation for immune response.
Analysis on the relationship between Effort- Reward imbalance and job satisfaction among family doctors in China: a cross-sectional study
Authors: Chen Jinhua , Wang Yijun , Du Wen , Liu Shuyi , Xiao Zhu , Wu Yuelei 
Published: April 2022

Abstract
Background: Family doctor contract services was launched in Sichuan province in 2016. The focus was mainly on developing primary health care services but paying less attention to the work stress and job satisfaction of in-service family doctors. Objective: This study aims to explore the influencing factors of job satisfaction, and the relation between work stress indicators and job satisfaction among family physicians. Methods: An analytical online cross-sectional survey was performed among 1,105 family doctors from 23 districts and counties in Chengdu. Self-administered questionnaire was completed. Sociodemographic factors, work stress measured by Effort-Reward Imbalance (ERI)scale, and job satisfaction assessed by the short Chinese version of the Minnesota Satisfaction Questionnaire (MSQ) were collected in this study. A statistical analysis and hierarchical linear regression analysis were performed to explore the influencing factors and the correlations among related variables. Results: The overall mean MSQ score was 52.01±13.23. Analysis of doctor satisfaction indicated that age, education, job rank, type of institution, years of working and monthly income were statistically significant (P<0.05). There were negative correlation coefficients between general job satisfaction and effort/reward ratio (ERR) (r=-0.130, P<0.001) and overcommitment (r=-0.615, P<0.001). Conclusion: The level of job satisfaction among family doctors was considerable low. Age, education, job rank, type of institution, years of working and monthly income were influencing factors of job satisfaction. ERI and overcommitment had a negative correlation with general job satisfaction.
Long-Term Clinical Outcomes of Oral Antidiabetic Drugs as Fixed-Dose Combinations: A Nationwide Retrospective Cohort Study
Authors: Cho Sang-Jun , Oh In-Sun , Jeong Han Eol , Cho Young Min , Hwangbo Yul , Yu Oriana Hoi Yun , Shin Ju-Young 
Published: April 2022

Abstract
Objectives: Patients with type 2 diabetes often require more than one medication for glycemic control. Although single pill fixed-dose combinations (FDC) might improve adherence, its impact on clinical outcomes remains unclear. We compared treatment patterns and clinical outcomes of FDC and two-pill combination (TPC) therapies using real-world data.Methods: We conducted a nationwide retrospective cohort study using South Korea’s healthcare database (2002–2015). We identified two cohorts of incident patients with type 2 diabetes who initiated FDC or TPC therapy within 4 months of their first prescription for metformin or sulfonylurea. We examined persistence and adherence patterns and the clinical outcome of a composite endpoint of death or hospitalization for acute myocardial infarction, heart failure, or stroke and compared the differences in treatment patterns and clinical outcomes using Cox models.Results: Of 5,143 and 10,974 patients who initiated FDC and TPC therapy, respectively, we identified 5,143 patient pairs after propensity score matching. The FDC group exhibited greater median time to treatment discontinuation (163 versus 146 days), and proportion of days covered (PDC) at 12 months (mean 0.60 versus 0.57, P < 0.0001) and at 24 months (0.53 versus 0.51, P=0.014) than the TPC group. The FDC group, compared with the TPC group, had reduced risks of the composite clinical outcome (hazard ratio 0.74, 95% confidence intervals 0.57–0.95) and hospitalization for stroke (0.68, 0.49–0.94).Conclusion: FDC therapy may provide favorable cardiovascular benefits, especially reducing the risk of hospitalization for stroke, and have better medication adherence among patients with type 2 diabetes.
Aspirin attenuates morphine antinociceptive tolerance in rats with diabetic neuropathy by inhibiting apoptosis in the dorsal root ganglia
Authors: Ozdemir Ercan , Avcı Onur , Inan Zeynep Deniz Sahin , Taskiran Ahmet Sevki , Gunes Handan , Gursoy Sinan 
Published: April 2022

Abstract
Morphine is a drug used in chronic pain such as diabetic neuropathy, but the development of tolerance to its antinociceptive effect is an important clinical problem. Recently, it has been stated that morphine-induced neuronal apoptosis can stimulate morphine tolerance. Our aim in this study was to investigate the effects of aspirin on morphine-induced neuronal apoptosis and analgesic tolerance in rats with diabetic neuropathy. After morphine tolerance induction, the antinociceptive effects of aspirin (50 mg/kg) and morphine (5 mg/kg) were evaluated by thermal pain tests at 15 or 30 minute intervals. Streptozotocin (STZ, 65 mg/kg) was injected intraperitoneally to induce diabetic neuropathy. To evaluate apoptosis in dorsal root ganglion (DRG) tissue, ELISA kits were used to measure caspase-3, Bax and Bcl-2 levels. Apoptotic cells were detected histologically by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method. Study results indicate that prior administration of aspirin to diabetic rats significantly increased the antinociceptive efficacy of morphine compared to morphine alone. Thermal pain tests showed that aspirin significantly reduced morphine tolerance in rats with diabetic neuropathy. Biochemical analysis revealed that aspirin significantly decreased the levels of pro-apoptotic proteins, caspase-3 and Bax, while increasing the anti-apoptotic Bcl-2 in DRG neurons. Semiquantitative scoring demonstrated that aspirin provided a significant reduction in apoptotic cell counts in diabetic rats. In conclusion, these data suggested that aspirin attenuated morphine antinociceptive tolerance through anti-apoptotic activity in diabetic rat DRG neurons. Further studies are needed to elucidate these effects of aspirin on morphine tolerance.
Evidence of SARS-CoV-2 reinfection: analysis of 35,000 subjects and overview of systematic reviews
Authors: Pecoraro Valentina , Pirotti Tommaso , Trenti Tommaso 
Published: April 2022

Abstract
Background: Reinfection by SARS-CoV-2 is a rare but possible event. We evaluated the prevalence of reinfections in the Province of Modena and performed an overview of systematic reviews to summarize the current knowledge.Methods: We applied big data analysis and retrospectively analysed the results of oro- or naso-pharyngeal swab results tested for molecular research of viral RNA of SARS-CoV-2 between 1 January 2021 to 30 June 2021 at a single center. We selected individuals with a samples sequence of positive, negative and then positive results. Between first and second positive result we considered a time interval of 90 days to be sure of a reinfection.We also performed a search for and evaluation of systematic reviews reporting SARS-CoV-2 reinfection rates. Main information was collected and the methodological quality of each review was assessed, according to A MeaSurement Tool to Assess systematic Reviews (AMSTAR). Results: Initial positive results were revealed in more than 35,000 (20%) subjects; most (28%) were aged 30-49 years old. Reinfection was reported in 1,258 (3.5%); most (33%) were aged 30-49 years old. Reinfection rates according to vaccinated or non-vaccinated subjects were 0.6% vs 1.1% (p<0.0001). Nine systematic reviews were identified and confirmed that SARS-CoV-2 reinfection rate is a rare event. AMSTAR revealed very low-moderate levels of quality among selected systematic reviews. Conclusions: There is a real, albeit rare risk of SARS-CoV-2 reinfection. Big data analysis enabled accurate estimates of the reinfection rates. Nevertheless, a standardized approach to identify and report reinfection cases should be developed.
A Message Passing framework with Multiple data integration for miRNA-Disease association prediction
Authors: Dong Thi Ngan , Schrader Johanna , Mücke Stefanie , Khosla Megha 
Published: April 2022

Abstract
Micro RNA or miRNA is a highly conserved class of non-coding RNA that plays an important role in many diseases. Identifying miRNA-disease associations can pave the way for better clinical diagnosis and finding potential drug targets. We propose a biologically-motivated data-driven approach for the miRNA-disease association prediction, which overcomes the data scarcity problem by exploiting information from multiple data sources. The key idea is to enrich the existing miRNA/disease-protein-coding gene (PCG) associations via a Message Passing framework, followed by the use of disease ontology information for further feature filtering. The enriched and filtered PCG associations are then used to construct the interconnected miRNA-PCG-disease network to train a structural deep network embedding (SDNE) model. Finally, the pre-trained embedding and the biologically relevant features from the miRNA family and disease semantic similarity are concatenated to form the pair input representation to a Random Forest classifier whose task is to predict the miRNA-disease association probability. We present large-scale comparative experiments, ablation, and case studies to showcase our approach’s superiority. Besides, we make the model prediction results for 1,618 miRNAs and 3,679 diseases, along with all related information publicly available at http://software.mpm.leibniz-ai-lab.de/index.html to foster assessments and future adoption.
Facile and mild preparation of brookite TiO2 nanoparticles with small sizes
Authors: Xu Jinlei , Yang Jingsi , Lu Hanhan , Mei Wenlong , Peng Tingxin 
Published: April 2022

Abstract
In this study, we used hydrothermal treatment with different metal cation as additive to prepare small size brookite TiO2 with large surface area. The obtained brookite nanoparticles is provided with both high crystal phase purity and smaller uniform particle size (∼10 nm). The small size brookite TiO2 as photoanode material of DSSCs retains the advantages of higher open-circuit voltage, and improvement of higher short-circuit current density by larger specific surface areas. It has best photoelectric conversion efficiency reached 6.48%, which is comparable to commercial P25. This research therefore provides a facile and mild synthetic method of small size brookite nanoparticles as excellent photoanode materials.
Biological difference between L858R and exon 19 deletion contributes to recurrence-free survival of resected non-small cell lung cancer
Authors: Masago Katsuhiro , Kuroda Hiroaki , Fujita Shiro , Sasaki Eiichi , Takahashi Yusuke , Shinohara Shuuichi , Matsushita Hirokazu 
Published: April 2022

Abstract
Background:The differences in biological characteristics among different genotypes of classical EGFR mutations have not been clarified. This study aims to clarify the clinical and biological differences between L858R and 19 deletion in NSCLC. Patients and Methods:We analyzed a cohort of 170 consecutive cases of surgically resected NSCLC harboring EGFR driver mutations (L858R or 19 deletion) in which curative resection was performed in Aichi Cancer Center Hospital, Nagoya, Japan from January 2006 to February 2013 and in which recurrence subsequently developed. We also subjected 61 surgically resected NSCLC specimens harboring EGFR driver mutations (L858R or 19 deletion) to an RNA sequencing analysis.Results:In patients with stage I and II disease, the median time to recurrence did not differ to a statistically significant extent between the types of EGFR mutations; however, among those with stage III disease, the median time to recurrence in patients with the L858R genotype tended to be shorter in comparison to those with 19 deletion (log-rank test, P = 0.071). In comparison to 19 deletion tumors, L858R tumors had higher cytological malignancy (e.g., mitotic ability) and showed stronger immunogenicity.Conclusions:L858R and 19 deletion tumors are likely to have a slight difference in the time to recurrence. They suggest that even in EGFR driver tumors, which are treated as the same disease category, the biological characteristics of the tumors are different, which may leave room for innovations in postoperative treatment and treatment at recurrence.
The effect of community-based intervention packages on common metabolic risk factors for non-communicable diseases: a field trial study
Authors: Asadi-Aliabadi Mehran , Karimi Seyed M , Mirbaha-Hashemi Fariba , Tehrani-Banihashemi Arash , Janani Leila , Babaee Ebrahim , Nojomi Marzieh , Moradi-Lakeh Maziar 
Published: April 2022

Abstract
Background: Non-communicable diseases can be controlled and managed by reducing their associated metabolic risk factors. In this study, a set of intervention packages were designed to reduce the prevalence of three common metabolic risk factors (hypertension, hyperlipidemia, and obesity and overweight) in the community by motivating non-physician health workers. Methods: A field trial study was conducted in 4 districts of Iran. Thirty-two community health centers were randomly selected in the districts. A survey of 30 to 70-year-old participants in each community health center was conducted to measure baseline metabolic risk factors. The intervention packages focused on improving hypertension, hyperlipidemia, obesity and overweight. The interventions included goal-setting, evidence-based education, operational planning, and incentive payments for non-physician health workers. A second survey to measure the final metabolic risk factors was performed after one year. The difference-in-difference method was used to evaluate the effectiveness of the intervention packages.Results: The average age of participants in both surveys was 49 years, and the sex ratio did not change. In percentage of surveyed individuals with a college education was greater in non-intervention centers. The interventions had statistically significant effects only on decreasing the prevalence of overweight and obesity. The package with all the interventions except pay-for-performance decreased the odds of overweight and obesity to 0.57 (95% CI: 0.34, 0.95). Conclusion: Involving non-physician health workers and having action plans based on the health needs of the covered population, as well as holding training courses, and introducing new prevention and control strategies, can decrease obesity and overweight in the community. However, longer trials are needed to observe the effects on hypertension and hyperlipidemia.Trial Registration: This trial was registered in the Iranian Registry of Clinical Trials (IRCT20081205001488N2) on 3 June 2018 (https://en.irct.ir/trial/774).
Correlations for Untargeted GC×GC-HRTOF-MS Metabolomics of Colorectal Cancer
Authors: Giovanni Nicolas , Meuwis Marie-Alice , Louis Edouard , Focant Jean-François 
Published: April 2022

Abstract
Introduction Modern comprehensive instrumentations provide an unprecedented coverage of complex matrices in the form of high-dimensional, information rich data sets. Objective In addition to the usual biomarker research that focuses on the detection of the studied condition, we aimed to define a proper strategy to conduct a correlation analysis on an untargeted colorectal cancer case study with a data set of 102 variables corresponding to metabolites obtained from serum samples analyzed with comprehensive two-dimensional gas chromatography coupled to high-resolution time-of-flight mass spectrometry (GC×GC-HRTOF-MS). Indeed, the strength of association existing between the metabolites contains potentially valuable information about the molecular mechanisms involved and the underlying metabolic network associated to a global perturbation, at no additional analytical effort. Methods Following Anscombe’s quartet, we took particular attention to four main aspects. First, the presence of non-linear relationships through the comparison of parametric and non-parametric correlation coefficients: Pearson’s r, Spearman’s rho, Kendall’s tau and Goodman-Kruskal’s gamma. Second, the visual control of the detected associations through scatterplots and their associated regressions and angles. Third, the effect and handling of atypical samples and values. Fourth, the role of the precision of the data on the attribution of the ranks through the presence of ties. Results Kendall’s tau was found the method of choice for the data set at hand. Its application highlighted 17 correlations significantly altered in the active state of colorectal cancer (CRC) in comparison to matched healthy controls (HC), from which 10 were specific to this state in comparison to the remission one (R-CRC) investigated on distinct patients. 15 metabolites involved in the correlations of interest, on the 25 unique ones obtained, were annotated (Metabolomics Standards Initiative level 2) Conclusions The metabolites highlighted could be used to better understand the pathology and the systematic investigation of the methodological aspects allows to implement correlation analysis to various fields and many specific cases.
Laboratory animal anesthesia classification (LAAC)
Authors: Ahmadi-Noorbakhsh Siavash 
Published: April 2022

Abstract
Anesthesia and analgesia (AA) are major components of animal research. However, various studies have shown an undesirable quality of AA reporting and use in research proposals and even high impact articles. Part of the problem may be related to a lack of special training in animal anesthesia among researchers. This causes an absence of a common language for AA among researchers, grant reviewers, ethics committees, animal welfare bodies, and journal reviewers. Herein, I present a laboratory animal anesthesia classification (LAAC) system that facilitates identification and grouping of various procedures requiring AA. The LAAC classes are developed according to the distress level and type of tissue injury caused by each procedure. Thereby, procedures causing similar types of pain or distress are grouped together and a certain AA approach could be applied to each group. LAAC classifies procedures into 12 classes and three categories with neuropathic pain being a separate component that could be added to each of the classes. Category A comprises LAAC1 to LAAC4 and requires no anesthesia. Category B is comprised of LAAC5 to LAAC8 and mainly includes non-surgical procedures. Category C includes surgical procedures classified under LAAC9 to LAAC12. Generally, a higher class of LAAC requires more potent AA regimen. In conclusion, LAAC provides a common language among various research bodies. A certain LAAC class conveys information regarding the nature of the same-group procedures and required intraoperative and postoperative AA for those procedures. LAAC also enables comparison of various procedures according to their nature and AA requirements.