bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pravastatin reduces plasma levels of extracellular vesicles in pregnancies at high risk of term preeclampsia
Authors: Santoyo Jean Michell , Noguera José Antonio , Avilés Francisco , Hernández-Caselles Trinidad , de Paco-Matallana Catalina , Delgado Juan Luis , Cuevas Santiago , Llinás M. Teresa , Hernández Isabel 
Published: June 2023

Introduction: Elevated plasma levels of extracellular vesicles have been associated with impaired placentation, angiogenesis imbalance, intravascular inflammation, and endothelial dysfunction in women with preeclampsia, thus suggesting that circulating vesicles may be a good therapeutic target for the treatment of the disease. Recently, statins have been considered a potential treatment for the prevention of preeclampsia because of their pleiotropic effects, including the improvement of endothelial dysfunction and inhibition of inflammatory responses. However, the effects of these drugs on circulating vesicles concentration in women at risk of preeclampsia have not been established. Herein, we aimed to assess the effects of pravastatin on circulating extracellular vesicle generation in women at high risk of term preeclampsia.Methods: In a sample of 68 singleton pregnant women participating in the multicenter, double-blind, placebo-controlled STATIN trial (Nº EducraCT 2016-005206-19 ISRCTN), 35 women received a placebo and 33 women received a 20 mg/day dose of pravastatin for approximately 3 weeks (from 35 to 37 weeks of gestation until delivery). Large extracellular vesicles were characterized and quantified by flow cytometry using annexin V and cell-specific antibodies directed against platelet, endothelial, leukocyte, and syncytiotrophoblast cell surface markers.Results: In women who received the placebo, a significant increase in the plasma levels of large extracellular vesicles from platelets (34%, p &lt; 0.01), leukocytes (33%, p &lt; 0.01), monocytes (60%, p &lt; 0.01), endothelial cells (40%, p &lt; 0.05), and syncytiotrophoblast cells (22%, p &lt; 0.05) were observed. However, treatment with pravastatin significantly reduced the plasma levels of large extracellular vesicles from platelets (42%, p &lt; 0.001), leukocytes (25%, p &lt; 0.001), monocytes (61%, p &lt; 0.001), endothelial cells (69%, p &lt; 0.001), activated endothelial cells (55%, p &lt; 0.001), and syncytiotrophoblast cells (44%, p &lt; 0.001).Discussion: These results indicate that pravastatin reduces the levels of activated cell-derived membrane vesicles from the maternal vasculature, blood, and placental syncytiotrophoblast of women at high risk of term preeclampsia, suggesting that this statin may be beneficial in reducing endothelial dysfunction and pro-inflammatory and pro-coagulatory state characteristics of the disease.
A randomized, open-label, parallel pilot study investigating metabolic product kinetics of the novel ketone ester, bis-hexanoyl (R)-1,3-butanediol, over one week of ingestion in healthy adults
Authors: Mah Eunice , Blonquist Traci M. , Kaden Valerie N. , Beckman Dawn , Boileau Amy C. , Anthony Joshua C. , Stubbs Brianna J. 
Published: June 2023

Introduction: Bis-hexanoyl (R)-1,3-butanediol (BH-BD) is a novel ketone ester that, when consumed, is hydrolyzed into hexanoic acid (HEX) and (R)-1,3-butanediol (BDO) which are subsequently metabolized into beta-hydroxybutyrate (BHB).Methods: We undertook a randomized, parallel, open-label study in healthy adults (n = 33) to elucidate blood BHB, HEX and BDO concentrations for 8 h following consumption of three different serving sizes (SS) of BH-BD (12.5, 25 and 50 g/day) before (Day 0) and after 7 days of daily BH-BD consumption (Day 7).Results: Maximal concentration and area under the curve of all metabolites increased proportionally to SS and were greatest for BHB followed by BDO then HEX on both Day 0 and 7. Metabolite half-life tended to decrease with increasing SS for BHB and HEX. Time to peak concentration increased with increasing SS for BHB and BDO on both days. In vitro incubation of BH-BD in human plasma demonstrated BH-BD undergoes rapid spontaneous hydrolysis.Conclusion: These results demonstrate that orally ingested BH-BD is hydrolyzed into products that appear in the plasma and undergo conversion to BHB in a SS dependent manner, and that metabolism of BH-BD neither becomes saturated at serving sizes up to 50 g nor displays consistent adaptation after 7 days of daily consumption.
Nitrogen reduction combined with ETc irrigation maintained summer maize yield and increased water and nitrogen use efficiency
Authors: Gu Limin , Mu Xinyuan , Qi Jianshuang , Tang Baojun , Zhen Wenchao , Xia Laikun 
Published: June 2023

IntroductionHigh rainfall and excessive urea application are counterproductive to summer maize growth requirements and lower grain yield and water/nitrogen (N) use efficiency. The objective of this study was to determine whether ETc irrigation based on summer maize demand and reduced nitrogen rate in the Huang Huai Hai Plain increased water and nitrogen use efficiency without sacrificing yield.MethodsTo achieve this, we conducted an experiment with four irrigation levels [ambient rainfall (I0) and 50% (I1), 75% (I2), and 100% (I3) of actual crop evapotranspiration (ETc)] and four nitrogen rates [no nitrogen fertilizer (N0), recommended nitrogen rate of urea (NU), recommended nitrogen rate of blending controlled-release urea with conventional urea fertilizer (BCRF) (NC), and reduced nitrogen rate of BCRF (NR)] in 2016–2018.ResultsThe results show that reduced irrigation and nitrogen rate reduced Fv/Fm, 13C-photosynthate, and nitrogen accumulation both in the kernel and plant. I3NC and I3NU accumulated higher 13C-photosynthate, nitrogen, and dry matter. However, 13C-photosynthate and nitrogen distribution to the kernel was decreased from I2 to I3 and was higher in BCRF than in urea. I2NC and I2NR promoted their distribution to the kernel, resulting in a higher harvest index. Compared with I3NU, I2NR increased root length density by 32.8% on average, maintaining considerable leaf Fv/Fm and obtaining similar kernel number and kernel weight. The higher root length density of I2NR of 40–60 cm promoted 13C-photosynthate and nitrogen distribution to the kernel and increased the harvest index. As a result, the water use efficiency (WUE) and nitrogen agronomic use efficiency (NAUE) in I2NR increased by 20.5%–31.9% and 11.0%–38.0% than that in I3NU, respectively.DiscussionTherefore, 75%ETc deficit irrigation and BCRF fertilizer with 80% nitrogen rate improved root length density, maintained leaf Fv/Fm in the milking stage, promoted 13C-photosynthate, and distributed nitrogen to the kernel, ultimately providing a higher WUE and NAUE without significantly reducing grain yield.
Genetic diversity and genome-wide association analysis of pine wood nematode populations in different regions of China
Authors: Aixia Yang , Xiaolei Ding , Yuan Feng , Ruiwen Zhao , Jianren Ye 
Published: June 2023

IntroductionPine wilt disease (Bursaphelenchus xylophilus) was recently detected in Liaoning Province, which was previously considered an unfavourable area for B. xylophilus due to its low temperatures. This study aims to compare the reproductivity and genetic variations of B. xylophilus isolates from Liaoning Province and other parts of China to explore their phenotypic and genomic differences.MethodsThe samples from Liaoning, Anhui, Hubei, Henan, Zhejiang and Jiangsu were isolated and purified to obtain the strains. The reproductivity of the strains was determined at 15 °C. The genetic structure was analyzed by using SNP molecular markers, and the whole genome association analysis was carried out by integrating SNP information and feculence traits.ResultsA reproductivity experiment showed that Liaoning isolates have higher reproductive ability at 15 °C. Subsequent SNP profiling and population differentiation analysis revealed obvious genetic differentiation of Liaoning isolates from other isolates. A genome-wide association study showed that SNPs closely related to low-temperature tolerance were mainly located in GPCR, Acyl-CoA, and Cpn10, which are responsible for adaptation to environmental factors, such as temperature change.DiscussionPine wood nematodes likely adapted to the climate in Liaoning and maintained a certain reproductive capacity at low temperature via variants of adaptation-related genes. This study provides a theoretical basis for elucidating the prevalence and diffusion status of B. xylophilus in China.
Identification and characterization of CYP71 subclade cytochrome P450 enzymes involved in the biosynthesis of bitterness compounds in Cichorium intybus
Authors: De Bruyn Charlotte , Ruttink Tom , Lacchini Elia , Rombauts Stephane , Haegeman Annelies , De Keyser Ellen , Van Poucke Christof , Desmet Sandrien , Jacobs Thomas B. , Eeckhaut Tom , Goossens Alain , Van Laere Katrijn 
Published: June 2023

Industrial chicory (Cichorium intybus var. sativum) and witloof (C. intybus var. foliosum) are crops with an important economic value, mainly cultivated for inulin production and as a leafy vegetable, respectively. Both crops are rich in nutritionally relevant specialized metabolites with beneficial effects for human health. However, their bitter taste, caused by the sesquiterpene lactones (SLs) produced in leaves and taproot, limits wider applications in the food industry. Changing the bitterness would thus create new opportunities with a great economic impact. Known genes encoding enzymes involved in the SL biosynthetic pathway are GERMACRENE A SYNTHASE (GAS), GERMACRENE A OXIDASE (GAO), COSTUNOLIDE SYNTHASE (COS) and KAUNIOLIDE SYNTHASE (KLS). In this study, we integrated genome and transcriptome mining to further unravel SL biosynthesis. We found that C. intybus SL biosynthesis is controlled by the phytohormone methyl jasmonate (MeJA). Gene family annotation and MeJA inducibility enabled the pinpointing of candidate genes related with the SL biosynthetic pathway. We specifically focused on members of subclade CYP71 of the cytochrome P450 family. We verified the biochemical activity of 14 C. intybus CYP71 enzymes transiently produced in Nicotiana benthamiana and identified several functional paralogs for each of the GAO, COS and KLS genes, pointing to redundancy in and robustness of the SL biosynthetic pathway. Gene functionality was further analyzed using CRISPR/Cas9 genome editing in C. intybus. Metabolite profiling of mutant C. intybus lines demonstrated a successful reduction in SL metabolite production. Together, this study increases our insights into the C. intybus SL biosynthetic pathway and paves the way for the engineering of C. intybus bitterness.
Transcriptomic and co-expression network analyses on diverse wheat landraces identifies candidate master regulators of the response to early drought
Authors: Barratt Liam J. , Reynolds Isaac J. , Franco Ortega Sara , Harper Andrea L. 
Published: June 2023

IntroductionOver four billion people around the world rely on bread wheat (Triticum aestivum L.) as a major constituent of their diet. The changing climate, however, threatens the food security of these people, with periods of intense drought stress already causing widespread wheat yield losses. Much of the research into the wheat drought response has centred on the response to drought events later in development, during anthesis or grain filling. But as the timing of periods of drought stress become increasingly unpredictable, a more complete understanding of the response to drought during early development is also needed.MethodsHere, we utilized the YoGI landrace panel to identify 10,199 genes which were differentially expressed under early drought stress, before weighted gene co-expression network analysis (WGCNA) was used to construct a co-expression network and identify hub genes in modules particularly associated with the early drought response.ResultsOf these hub genes, two stood out as novel candidate master regulators of the early drought response – one as an activator (TaDHN4-D1; TraesCS5D02G379200) and the other as a repressor (uncharacterised gene; TraesCS3D02G361500).DiscussionAs well as appearing to coordinate the transcriptional early drought response, we propose that these hub genes may be able to regulate the physiological early drought response due to potential control over the expression of members of gene families well-known for their involvement in the drought response in many plant species, namely dehydrins and aquaporins, as well as other genes seemingly involved in key processes such as, stomatal opening, stomatal closing, stomatal morphogenesis and stress hormone signalling.
Children’s bond with companion animals and associations with psychosocial health: A systematic review
Authors: Groenewoud Daniëlle , Enders-Slegers Marie-Jose , Leontjevas Roeslan , van Dijke Annemiek , de Winkel Tynke , Hediger Karin 
Published: June 2023

BackgroundCompanion animals can fulfill children’s attachment needs. A secure attachment to humans is positively associated with psychosocial health, therefore, the extent to which this applies to a strong child-companion animal bond is worth examining.AimsWe aimed to gain insight into the current literature regarding the bond between children and companion animals and psychosocial health. Secondary, we also synthesized evidence about the (1) characteristics of children and companion animals and the strength of their bond; (2) the correlations between attachment to humans and the child-companion animal bond; and (3) the instruments used to measure the child-companion animal bond.MethodAccording to PRISMA guidelines, we searched three major electronic databases (PubMed, EBSCOhost, and Web of Science) in September 2021 and included records with the following criteria: peer reviewed English articles with quantitative and qualitative data on child-companion animal bonds and children’s psychosocial health. Reports with participants younger than 18 years of age with a family owned companion animal were included. Two authors performed the screening and determined eligibility according to a predefined coding protocol.ResultsThe search revealed 1,025 unique records, of which we included 29 studies. Some positive associations were reported between the strength of the child-companion animal bond and children’s psychosocial health outcomes like empathy, social support, and quality of life, although some results were contradictory. We found differences in associations between a child’s gender, companion animal species and the strength of the child-companion animal bond. A secure attachment style to parents was positively associated with a stronger child–companion animal bond. Most of the instruments currently used, measure the strength of the bond.DiscussionThis review suggests that the child-companion animal bond could be beneficial for children’s psychosocial health, but some results were inconclusive. Also, not every relationship develops into an attachment. Since a strong bond with animals might not be the same as a secure attachment, we advise to modify human attachment instruments, in order to effectively study children’s attachment to companion animals. Lastly, research designs that are able to investigate the causality of the relationship between the child-companion animal bond and psychosocial health are required.
What happens when a whole-school health promotion research trial ends? a case study of the SEHER program in India
Authors: Shinde Sachin , Raniti Monika , Sharma Amit , Sawyer Susan M. 
Published: June 2023

BackgroundHealth promotion interventions that are developed and evaluated by researchers and other external providers are at risk of not being sustained beyond the initial implementation period. When delivered by a lay school health worker, the SEHER study of a whole-school health promotion intervention in Bihar, India was found to be feasible, acceptable and effective in improving school climate and student health behaviors. The objective of this case study is to describe the decision-making processes, barriers, and enablers to continuing the SEHER intervention following its official closure.MethodsFor this exploratory qualitative case study, data were collected from four government-run secondary schools, two of which continued SEHER and two of which discontinued it after official closure. Thirteen school staff were interviewed, and 100 girls and boys (aged 15–18  years old) participated in eight focus groups discussing their experiences of the process of continuing the intervention (or discontinuing) following its official closure. Thematic analysis was conducted in NVivo 12 using grounded theory.ResultsNo school sustained the intervention as originally delivered in the research trial. In two schools, the intervention was adapted by selecting sustainable components, whereas in two others it was discontinued altogether. We identified four interrelated themes that explained the complex decision-making process, barriers, and enablers related to program continuation: (1) understanding of the intervention philosophy among school staff; (2) school capabilities to continue with intervention activities; (3) school attitudes and motivation about implementing the intervention, and; (4) the education policy environment and governance structures. Suggestions for overcoming barriers included adequate resource allocation; training, supervision, and support from external providers and the Ministry of Education; and formal government approval to continue the intervention.ConclusionSustaining this whole-school health promotion intervention in low-resource school settings in India depended on individual, school and government factors as well as external support. These findings suggest that health interventions will not necessarily become embedded in a school’s operations merely because they are designed as a whole-school approach or because they are effective. Research should identify the resources and processes required to balance planning for future sustainability while awaiting trial results about an intervention’s effectiveness.
Shared genetics and causal relationships between major depressive disorder and COVID-19 related traits: a large-scale genome-wide cross-trait meta-analysis
Authors: Li Ziqi , Dang Weijia , Hao Tianqi , Zhang Hualin , Yao Ziwei , Zhou Wenchao , Deng Liufei , Yu Hongmei , Wen Yalu , Liu Long 
Published: June 2023

IntroductionThe comorbidity between major depressive disorder (MDD) and coronavirus disease of 2019 (COVID-19) related traits have long been identified in clinical settings, but their shared genetic foundation and causal relationships are unknown. Here, we investigated the genetic mechanisms behind COVID-19 related traits and MDD using the cross-trait meta-analysis, and evaluated the underlying causal relationships between MDD and 3 different COVID-19 outcomes (severe COVID-19, hospitalized COVID-19, and COVID-19 infection).MethodsIn this study, we conducted a comprehensive analysis using the most up-to-date and publicly available GWAS summary statistics to explore shared genetic etiology and the causality between MDD and COVID-19 outcomes. We first used genome-wide cross-trait meta-analysis to identify the pleiotropic genomic SNPs and the genes shared by MDD and COVID-19 outcomes, and then explore the potential bidirectional causal relationships between MDD and COVID-19 outcomes by implementing a bidirectional MR study design. We further conducted functional annotations analyses to obtain biological insight for shared genes from the results of cross-trait meta-analysis.ResultsWe have identified 71 SNPs located on 25 different genes are shared between MDD and COVID-19 outcomes. We have also found that genetic liability to MDD is a causal factor for COVID-19 outcomes. In particular, we found that MDD has causal effect on severe COVID-19 (OR = 1.832, 95% CI = 1.037–3.236) and hospitalized COVID-19 (OR = 1.412, 95% CI = 1.021–1.953). Functional analysis suggested that the shared genes are enriched in Cushing syndrome, neuroactive ligand-receptor interaction.DiscussionOur findings provide convincing evidence on shared genetic etiology and causal relationships between MDD and COVID-19 outcomes, which is crucial to prevention, and therapeutic treatment of MDD and COVID-19.
A pilot study on improvements in attention function in major depressive disorder after 12 weeks of escitalopram monotherapy or combined treatment with agomelatine
Authors: Li Zhe , Wu Ting-Ting , Xiong Yi-Ting , Zhang Xin-Yang , Bao Yan-Ping , Guo Li-Bo , Han Bao-Jie , Li Su-Xia , Wang Yu-Feng , Lu Lin , Wang Xue-Qin 
Published: June 2023

ObjectiveThis study aimed to explore both impairments in attention function in patients with major depressive disorder (MDD) and the efficacy of escitalopram monotherapy or combination therapy with agomelatine.MethodsA total of 54 patients with MDD and 46 healthy controls (HCs) were included. Patients were treated with escitalopram for 12 weeks; those who presented with severe sleep impairments were also given agomelatine. Participants were evaluated using the Attention Network Test (ANT), which included tests of alerting, orienting, and executive control networks. Concentration, instantaneous memory, and resistance to information interference were tested using the digit span test, and the logical memory test (LMT) was used to evaluate abstract logical thinking. The Hamilton Depression Rating Scale−17 items, Hamilton Anxiety Rating Scale, and Pittsburgh Sleep Quality Index were used to assess depression, anxiety, and sleep quality, respectively. Patients with MDD were assessed at the end of weeks 0, 4, 8, and 12. HCs were assessed once at baseline.ResultsCompared with HCs, patients with MDD showed significantly different alerting, orienting, and executive control functions of attention networks. Treatment with escitalopram alone or combined with agomelatine significantly improved LMT scores at the end of weeks 4, 8, and 12 and restored scores to the level of HCs at the end of week 8. Total Toronto Hospital Test of Alertness scores in patients with MDD increased significantly after 4 weeks of treatment. The ANT executive control reaction time in patients with MDD decreased significantly after 4 weeks of treatment, with this decrease lasting until the end of week 12, but scores did not return to the levels of HCs. Combined treatment with escitalopram and agomelatine led to more improvement in ANT orienting reaction time and was accompanied by a greater reduction of total scores on the Hamilton Depression Rating Scale−17 items and Hamilton Anxiety Rating Scale compared with escitalopram monotherapy.ConclusionsPatients with MDD showed overall impairments in three domains of attention networks as well as the LMT and a test of subjective alertness. Escitalopram monotherapy significantly improved the LMT scores and the executive control function scores in the ANT at the end of the fourth week of treatment, and the improvement was more extensive with combined escitalopram and agomelatine treatment.