bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the causal pathway from ischemic stroke to atrial fibrillation: a network Mendelian randomization study
Authors: Hou Lei , Xu Mingqing , Yu Yuanyuan , Sun Xiaoru , Liu Xinhui , Liu Lu , Li Yunxia , Yuan Tonghui , Li Wenchao , Li Hongkai , Xue Fuzhong 
Published: January 2020

Abstract
Background and purpose
Previous studies have found ischemic stroke is associated with atrial fibrillation. However, the causal association between ischemic stroke and atrial fibrillation is not clear. Furthermore, the network relationship among ischemic stroke, atrial fibrillation and its risk factors need further attention. This study aims to examine the potential causal association between ischemic stroke and atrial fibrillation and further to explore potential mediators in the causal pathway from ischemic stroke to atrial fibrillation.

Methods
Summary statistics from the ISGC (case = 10,307 and control = 19,326) were used as ischemic stroke genetic instruments, AFGen Consortium data (case = 65,446 and control = 522,744) were used for atrial fibrillation, and other consortia data were used for potential mediators (fasting insulin, white blood cell count, procalcitonin, systolic and diastolic blood pressure, body mass index, waist circumference, and height). Under the framework of network Mendelian randomization, two-sample Mendelian randomization study was performed using summary statistics from several genome-wide association studies. Inverse-variance weighted method was performed to estimate causal effect.

Results
Blood pressure mediates the causal pathways from ischemic stroke to atrial fibrillation. The total odds ratio of ischemic stroke on atrial fibrillation was 1.05 (95% confidence interval [CI], 1.02 to 1.07; P = 1.3 × 10−5). One-unit increase of genetically determined ischemic stroke was associated with 0.02 (DBP: 95% CI, 0.001 to 0.034, P = 0.029; SBP: 95% CI, 0.006 to 0.034, P = 0.003) upper systolic and diastolic blood pressure levels. Higher genetically determined systolic and diastolic blood pressure levels were associated with higher atrial fibrillation risk (DBP: RR, 1.18; 95% CI, 1.03 to 1.35; P = 0.012. SBP: RR, 1.18; 95% CI, 1.01 to 1.38; P = 0.04). Specially, we also found the bidirectional causality between blood pressure and ischemic stroke.

Conclusions
Our study provided a strong evidence that raised blood pressure in stroke patients increases the risk of atrial fibrillation and active acute blood pressure lowering can improve the outcome in ischemic stroke patients.
Association between standardized vitamin 25(OH)D and dyslipidemia: a community-based study in Riyadh, Saudi Arabia
Authors: AlQuaiz AlJohara M , Kazi Ambreen , Youssef Randa M. , Alshehri Norah , Alduraywish Shatha Ahmed 
Published: January 2020

Abstract
Background
Vitamin D deficiency associated with dyslipidemia can contribute towards cardiovascular diseases. Previous studies have found that Saudi Arabia has a high burden of vitamin D deficiency and cardiovascular disease risk factors. We aimed to explore the relationship between vitamin D deficiency and dyslipidemia, including total cholesterol, low-density lipids, high-density lipids (HDL), and triglycerides (TG) in apparently healthy Saudi male and female participants aged 30–75 years.

Methods
A cross-sectional study was conducted on 1717 apparently healthy Saudi participants from 18 primary health care centers in Riyadh. Data collectors conducted the interviews, took anthropometric measurements, and collected the blood samples. Serum 25-hydroxyvitamin vitamin D (25(OH)D) levels were measured using an electrochemiluminescence assay method. Lipid panel was measured by a fully automated analyzer using enzymatic methods.

Results
Multivariable logistic regression analysis revealed that the adjusted odds ratio (ORA) of low level of HDL cholesterol in association with 25(OH)D deficiency was 2.1 times higher in males (ORA = 2.1; 95% CI = 1.1, 3.9) and 1.3 times higher in females (ORA = 1.3; 95% CI = 0.9, 1.9). A significant excess odds ratio of high levels of TG in association with 25(OH) D deficiency was observed in females (ORA = 3.0; 95% CI = 1.1, 7.9) but not in males.

Conclusion
Vitamin D deficiency is highly prevalent in Saudi Arabia. Low levels of HDL cholesterol in men and high TG levels in women are associated with vitamin D deficiency. The results emphasize the importance of treating vitamin D deficiency in the general population.
The effects of the DNA Demethylating reagent, 5-azacytidine on SMCHD1 genomic localization
Authors: Massah S. , Jubene J. , Lee F. J. S. , Beischlag T. V. , Prefontaine G. G. 
Published: January 2020

Abstract
Background
DNA methylation is an epigenetic modification that mainly repress expression of genes essential during embryogenesis and development. There are key ATPase-dependent enzymes that read or write DNA methylation to remodel chromatin and regulate gene expression. Structural maintenance of chromosome hinge domain containing 1 (SMCHD1) is an architectural protein that regulates expression of numerous genes, some of which are imprinted, that are sensitive to DNA methylation. In addition, SMCHD1 germline mutations lead to developmental diseases; facioscapulohumoral muscular dystrophy (FSHD), bosma arhinia and micropthalmia (BAMS). Current evidence suggests that SMCHD1 functions through maintenance or de novo DNA methylation required for chromatin compaction. However, it is unclear if DNA methylation is also essential for genomic recruitment of SMCHD1 and its role as an architectural protein. We previously isolated SMCHD1 using a methylated DNA region from mouse pituitary growth hormone (Gh1) promoter, suggesting that methylation is required for SMCHD1 DNA binding. The goal of this study was to further understand DNA methylation directed role of SMCHD1 in regulating gene expression. Therefore, we profiled SMCHD1 genome wide occupancy in human neuroblastoma SH-SY5Y cells and evaluated if DNA methylation is required for SMCHD1 genomic binding by treating cells with the DNA demethylating reagent, 5-azacytidine (5-azaC).

Results
Our data suggest that the majority of SMCHD1 binding occurs in intron and intergenic regions. Gene ontology analysis of genes associated with SMCHD1 genomic occupancy that is sensitive to 5-azaC treatment suggests SMCHD1 involvement in central nervous system development. The potassium voltage-gated channel subfamily Q member1 (KCNQ1) gene that associates with central nervous system is a known SMCHD1 target. We showed SMCHD1 binding to an intronic region of KCNQ1 that is lost following 5-azaC treatment suggesting DNA methylation facilitated binding of SMCHD1. Indeed, deletion of SMCHD1 by CRISPR- Cas9 increases KCNQ1 gene expression confirming its role in regulating KCNQ1 gene expression.

Conclusion
These findings provide novel insights on DNA methylation directed function of SMCHD1 in regulating expression of genes associated with central nervous system development that impact future drug development strategies.
Transcriptome analysis of Clinopodium gracile (Benth.) Matsum and identification of genes related to Triterpenoid Saponin biosynthesis
Authors: Shan Chunmiao , Wang Chenkai , Zhang Shengxiang , Shi Yuanyuan , Ma Kelong , Yang Qingshan , Wu Jiawen 
Published: January 2020

Abstract
Background
Clinopodium gracile (Benth.) Matsum (C. gracile) is an annual herb with pharmacological properties effective in the treatment of various diseases, including hepatic carcinoma. Triterpenoid saponins are crucial bioactive compounds in C. gracile. However, the molecular understanding of the triterpenoid saponin biosynthesis pathway remains unclear.

Results
In this study, we performed RNA sequencing (RNA-Seq) analysis of the flowers, leaves, roots, and stems of C. gracile plants using the BGISEQ-500 platform. The assembly of transcripts from all four types of tissues generated 128,856 unigenes, of which 99,020 were mapped to several public databases for functional annotation. Differentially expressed genes (DEGs) were identified via the comparison of gene expression levels between leaves and other tissues (flowers, roots, and stems). Multiple genes encoding pivotal enzymes, such as squalene synthase (SS), or transcription factors (TFs) related to triterpenoid saponin biosynthesis were identified and further analyzed. The expression levels of unigenes encoding important enzymes were verified by quantitative real-time PCR (qRT-PCR). Different chemical constituents of triterpenoid saponins were identified by Ultra-Performance Liquid Chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS).

Conclusions
Our results greatly extend the public transcriptome dataset of C. gracile and provide valuable information for the identification of candidate genes involved in the biosynthesis of triterpenoid saponins and other important secondary metabolites.
Genome-resolved metagenomics analysis provides insights into the ecological role of Thaumarchaeota in the Amazon River and its plume
Authors: Pinto Otávio H. B. , Silva Thais F. , Vizzotto Carla S. , Santana Renata H. , Lopes Fabyano A. C. , Silva Bruno S. , Thompson Fabiano L. , Kruger Ricardo H. 
Published: January 2020

Abstract
Background
Thaumarchaeota are abundant in the Amazon River, where they are the only ammonia-oxidizing archaea. Despite the importance of Thaumarchaeota, little is known about their physiology, mainly because few isolates are available for study. Therefore, information about Thaumarchaeota was obtained primarily from genomic studies. The aim of this study was to investigate the ecological roles of Thaumarchaeota in the Amazon River and the Amazon River plume.

Results
The archaeal community of the shallow in Amazon River and its plume is dominated by Thaumarchaeota lineages from group 1.1a, which are mainly affiliated to Candidatus Nitrosotenuis uzonensis, members of order Nitrosopumilales, Candidatus Nitrosoarchaeum, and Candidatus Nitrosopelagicus sp. While Thaumarchaeota sequences have decreased their relative abundance in the plume, Candidatus Nitrosopelagicus has increased. One genome was recovered from metagenomic data of the Amazon River (ThauR71 [1.05 Mpb]), and two from metagenomic data of the Amazon River plume (ThauP25 [0.94 Mpb] and ThauP41 [1.26 Mpb]). Phylogenetic analysis placed all three Amazon genome bins in Thaumarchaeota Group 1.1a. The annotation revealed that most genes are assigned to the COG subcategory coenzyme transport and metabolism. All three genomes contain genes involved in the hydroxypropionate/hydroxybutyrate cycle, glycolysis, tricarboxylic acid cycle, oxidative phosphorylation. However, ammonia-monooxygenase genes were detected only in ThauP41 and ThauR71. Glycoside hydrolases and auxiliary activities genes were detected only in ThauP25.

Conclusions
Our data indicate that Amazon River is a source of Thaumarchaeota, where these organisms are important for primary production, vitamin production, and nitrification.
Prevalence and antimicrobial susceptibility of enterotoxigenic extra-intestinal Bacteroides fragilis among 13-year collection of isolates in Kuwait
Authors: Jamal Wafaa , Khodakhast Fatima Bibi , AlAzmi Ameerah , Sόki Jόzsef , AlHashem Ghayda , Rotimi Vincent O. 
Published: January 2020

Abstract
Background
Some strains of Bacteroides fragilis species are associated with diarrhea as a result of enterotoxin production (bft or fragilysin). Fragilysin is activated by C11 protease (fpn) and together with C10 protease (bfp) play a significant role in its invasiveness. The objectives of this study were to investigate the proportion of clinical isolates from extra-intestinal sources that are toxin producers and characterize the genes mediating toxin production. Clinical isolates submitted to our reference laboratory over the last 13 years were screened for toxin production using PCR technique. All stool isolates were excluded. The isolates were tested for their susceptibility to 8 antimicrobial agents by E test. Carbapenem resistance gene cfiA was detected by PCR.

Results
A total of 421 B. fragilis isolates were viable. Out of these, bft was detected in 210 (49.9%) isolates. Of the 210 bft-positive isolates, 171 (81.4%), 33 (15.7%) and 6 (2.8%) harbored bft-1, bft-2, and bft-3 genes, respectively. Twenty (9.5%) of the bft-positive strains originated from bloodstream infections. Twenty-five, 20 and 9 strains harbored bfp-1, bfp-2 and bfp-3 gene, respectively. Two, 3, 4 bfp isotypes were detected simultaneously in some of strains. The resistance rates against amoxicillin-clavulanic acid was 32%, clindamycin 62%, cefoxitin 26%, imipenem 11%, meropenem 17%, metronidazole 4%, piperacillin 61% and tigecycline 14%. A chromosomally located cfiA gene that encode metallo-β-lactamase was identified in only 34 isolates (16.2%).

Conclusions
The prevalence of enterotoxin-producing B. fragilis was high among the extra-intestinal isolates. Metronidazole was the most active agent against all isolates. There was no statistically significance difference between resistance rates among bft-positive and bft-negative isolates except for clindamycin.
Folic acid ameliorates depression-like behaviour in a rat model of chronic unpredictable mild stress
Authors: Zhou Yue , Cong Yu , Liu Huan 
Published: January 2020

Abstract
Background
Depression is characterized by significant and low mood. Classical antidepressants are still not adequate in treating depression because of undesirable side effects. Folic acid, a member of the vitamin B complex, in considered to be strongly associated with the function and development of the central nervous system. Thus, in this study, we established a model of depression through chronic unpredictable mild stress (CUMS) in rats and assessed the antidepressant effects and mechanisms of folic acid.

Methods
Sprague–Dawley rats were randomly divided into four groups: control, chronic unpredictable mild stress (CUMS), CUMS treated with folic acid, and CUMS treated with citalopram. Rats were assessed in terms of weight change, open-field test and sucrose preference. Homocysteine, monoamine neurotransmitters, interleukin-6, brain-derived neurotrophic factor (BDNF), β-endorphin levels in the serum and brains of rats were analysed.

Results
Folic acid exhibited antidepressant-like effects in open-field and sucrose preference tests. Folic acid treatment effectively increased the levels of monoamine neurotransmitters, BDNF and β-endorphin, interleukin-6 and homocysteine levels were also significantly suppressed by folic acid administration.

Conclusions
These findings serve as preclinical evidence that folic acid plays an antidepressant-like role in several pathways involving monoamine neurotransmitters. Thus, folic acid may be used as a potential antidepressant.
Full moonlight-induced circadian clock entrainment in Coffea arabica
Authors: Breitler J-C. , Djerrab D. , Leran S. , Toniutti L. , Guittin C. , Severac D. , Pratlong M. , Dereeper A. , Etienne H. , Bertrand B. 
Published: January 2020

Abstract
Background
It is now well documented that moonlight affects the life cycle of invertebrates, birds, reptiles, and mammals. The lunisolar tide is also well-known to alter plant growth and development. However, although plants are known to be very photosensitive, few studies have been undertaken to explore the effect of moonlight on plant physiology.

Results
Here for the first time we report a massive transcriptional modification in Coffea arabica genes under full moonlight conditions, particularly at full moon zenith and 3 h later. Among the 3387 deregulated genes found in our study, the main core clock genes were affected.

Conclusions
Moonlight also negatively influenced many genes involved in photosynthesis, chlorophyll biosynthesis and chloroplast machinery at the end of the night, suggesting that the full moon has a negative effect on primary photosynthetic machinery at dawn. Moreover, full moonlight promotes the transcription of major rhythmic redox genes and many heat shock proteins, suggesting that moonlight is perceived as stress. We confirmed this huge impact of weak light (less than 6 lx) on the transcription of circadian clock genes in controlled conditions mimicking full moonlight.
Job satisfaction, burnout, and turnover intention among primary care providers in rural China: results from structural equation modeling
Authors: Wang Haipeng , Jin Yinzi , Wang Dan , Zhao Shichao , Sang Xingang , Yuan Beibei 
Published: January 2020

AbstractBackgroundLow job satisfaction, severe burnout and high turnover intention are found to be prevalent among the primary care providers (PCPs) in township health centers (THCs), but their associations have received scant attention in the literature. In light of this, this study aims to examine the relationships between job satisfaction, burnout and turnover intention, and explore the predictors of turnover intention with a view to retaining PCPs in rural China.MethodsUsing the multistage cluster sampling method, a cross-sectional survey was conducted in Shandong Province, China. 1148 PCPs from 47 THCs participated in this study. Job satisfaction, burnout and turnover intention were measured with a multifaceted instrument developed based on the existing literature, the Maslach Burnout Inventory and the participants’ responses to a Likert item drawn from the literature, respectively. The relationships of the three factors were examined using Pearson correlation and structural equation modeling, while the predictors of turnover intention were investigated using multivariate logistic regression.ResultsThe subscale that the PCPs were most dissatisfied with was job rewards (95.12%), followed by working environment (49.65%) and organizational management (47.98%). The percentages of the PCPs reporting high-levels of emotional exhaustion, depersonalization and reduced personal accomplishment were 27.66, 6.06, and 38.74%, respectively. About 14.06% of the respondents had high turnover intention. There was a significant direct effect of job satisfaction on burnout (γ = − 0.52) and turnover intention (γ = − 0.29), a significant direct effect of burnout on turnover intention (γ = 0.28), and a significant indirect effect (γ = − 0.14) of job satisfaction on turnover intention through burnout as a mediator. Work environment satisfaction, medical practicing environment satisfaction, and organizational management satisfaction proved to be negative predictors of turnover intention (p < 0.05), whereas reduced personal accomplishment was identified as a positive predictor (p < 0.05).ConclusionsPlagued by low job satisfaction and severe burnout, the PCPs in rural China may have high turnover intentions. Job satisfaction had not only negative direct effects on burnout and turnover intention, but also an indirect effect on turnover intention through burnout as a mediator. Targeted strategies should be taken to motivate and retain the PCPs.
The importance of different frailty domains in a population based sample in England
Authors:   on behalf of the Pre-FIT Study Group, Arnadottir Solveig A. , Bruce Julie , Lall Ranjit , Withers Emma J. , Underwood Martin , Shaw Fiona , Sheridan Ray , Hossain Anower , Lamb Sarah E. 
Published: January 2020

Abstract
Background
The aim was to estimate the prevalence of frailty and relative contribution of physical/balance, nutritive, cognitive and sensory frailty to important adverse health states (falls, physical activity levels, outdoor mobility, problems in self-care or usual activities, and lack of energy or accomplishment) in an English cohort by age and sex.

Methods
Analysis of baseline data from a cohort of 9803 community-dwelling participants in a clinical trial. The sample was drawn from a random selection of all people aged 70 or more registered with 63 general practices across England. Data were collected by postal questionnaire. Frailty was measured with the Strawbridge questionnaire. We used cross sectional, multivariate logistic regression to estimate the association between frailty domains and known correlates and adjusted for age. Some models were stratified by sex.

Results
Mean age of participants was 78 years (sd 5.7), range 70 to 101 and 47.5% (4653/9803) were men. The prevalence of overall frailty was 20.7% (2005/9671) and there was no difference in prevalence by sex (Odds Ratio 0.98; 95% Confidence Interval 0.89 to 1.08). Sensory frailty was the most common and this was reported by more men (1823/4586) than women (1469/5056; Odds Ratio for sensory frailty 0.62, 95% Confidence Interval 0.57 to 0.68). Men were less likely than women to have physical or nutritive frailty. Physical frailty had the strongest independent associations with adverse health states. However, sensory frailty was independently associated with falls, less frequent walking, problems in self-care and usual activities, lack of energy and accomplishment.

Conclusions
Physical frailty was more strongly associated with adverse health states, but sensory frailty was much more common. The health gain from intervention for sensory frailty in England is likely to be substantial, particularly for older men. Sensory frailty should be explored further as an important target of intervention to improve health outcomes for older people both at clinical and population level.

Trial registration
ISRCTN71002650.
Lymphedema in three previously Wuchereria bancrofti-endemic health districts in Mali after cessation of mass drug administration
Authors: Dolo Housseini , Coulibaly Yaya Ibrahim , Konipo Fatoumata Nene , Coulibaly Siaka Yamoussa , Doumbia Salif Seriba , Sangare Moussa Brema , Soumaoro Lamine , Coulibaly Michel Emmanuel , Diallo Abdallah Amadou , Diarra Yaye , Sangare Modibo , Doumbia Seydou , Colebunders Robert , Nutman Thomas B. 
Published: January 2020

AbstractBackgroundLymphedema is a public health problem in countries with lymphatic filariasis (LF) including Mali. We studied the epidemiology and clinical presentation of lymphedema in three previously LF-endemic health districts of Mali after at least five consecutive rounds of mass drug administration (MDA) with albendazole and ivermectin.MethodsFrom 2016 to 2018, we used passive and active case finding methods to identify lymphedema cases in three health districts with high pre-MDA LF prevalence: Kolondieba (66%), Bougouni (44%) and Kolokani (34%).ResultsThree hundred and thirty nine cases of lymphedema were identified, 235 (69.32%) through active case finding. Their median age was 56 years (range 2–90) and 286 (84.36%) were women. Lymphedema was reported in 226 (78.5%) people aged 41 years and older compared to 73 (21.5%) people below the age of 41 years (Chi2 = 17.28, df = 5,p = 0.004). One hundred and seventy five cases of lymphedema were found in Kolondieba (66 per 100,000 people), 116 in Bougouni (19 per 100,000) and 48 in Kolokani (16 per 100,000). Stage III lymphedema was observed in 131 (38.64%), stage II in 108 (31.86%), stage IV in 46 (13.57%), stage I in 23 (6.78%), stage V in 21 (6.19%) and stage VI in ten (2.95%). In the three study districts, lymphedema affected the legs in 281 (82.89%), the arms in 42 (12.39%) and both in 16 (4.72%) (Chi2 = 13.63,p = 0.008).ConclusionHealth districts in Mali with the highest pre-MDA LF prevalences had the highest prevalence of lymphedema. Efforts to actively identify lymphedema cases should be scaled up in previous LF-endemic areas, and should be supplemented by a morbidity management and disability prevention plan at the peripheral health system level.