bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative study of the effects of the three kinds of Kampo-hozai: Ninjinyoeito, Hochuekkito, and Juzentaihoto on anxious and low sociability behavior using NPY-knockout zebrafish
Authors: Kawabe Momoko , Nishida Takumi , Takahashi Ryuji , Inui Akio , Shiozaki Kazuhiro 
Published: June 2023

Ninjinyoeito, Hochuekkito, and Juzentaihoto are the three types of Kampo-hozai used to support the treatment of various diseases by energizing patients through improved mental health. While Kampo-hozais are clinically used to improve mental energy decline, a comparison between their effects on neuropsychiatric symptoms like anxiety and sociability and the strength of their effects has not been conducted. Therefore, this study compared the effects of Ninjinyoeito, Hochuekkito, and Juzentaihoto on psychiatric symptoms using neuropeptide Y knockout (NPY-KO) zebrafish, a suitable animal model for anxiety and low sociability. Neuropeptide Y knockout zebrafish were fed a Ninjinyoeito, Hochuekkito, or Juzentaihoto-supplemented diet for 4 days. Then, sociability was analyzed using a three-Chambers test and anxiety-like behavior was evaluated using the cold stress and novel tank tests. The results showed that Ninjinyoeito treatment improved the low sociability of neuropeptide Y knockout, while Hochuekkito and Juzentaihoto did not. Neuropeptide Y knockout exhibited anxiety-like behaviors, such as freezing and swimming in the wall area under cold stress, but Ninjinyoeito treatment improved these behaviors. However, these anxiety-like behaviors were not improved by Hochuekkito and Juzentaihoto. Ninjinyoeito treatment also improved anxiety-like behaviors of neuropeptide Y knockout in the novel tank test. However, no improvement was shown in the Hochuekkito and Juzentaihoto groups. This trend was also confirmed in the low water stress test using wild-type zebrafish. This study exhibits that among the three types of Kampo-hozai, Ninjinyoeito is the most effective in psychiatric disorders associated with anxiety and low sociability.
Investigation of adenosine A1 receptor-mediated β-arrestin 2 recruitment using a split-luciferase assay
Authors: Saecker Luisa , Häberlein Hanns , Franken Sebastian 
Published: June 2023

Background: Adenosine A1 receptor (A1AR) plays a prominent role in neurological and cardiac diseases and inflammatory processes. Its endogenous ligand adenosine is known to be one of the key players in the sleep–wake cycle. Like other G protein-coupled receptors (GPCRs), stimulation of A1AR leads to the recruitment of arrestins in addition to the activation of G proteins. So far, little is known about the role of these proteins in signal transduction and regulation of A1AR compared to the activation of G proteins. In this work, we characterized a live cell assay for A1AR-mediated β-arrestin 2 recruitment. We have applied this assay to a set of different compounds that interact with this receptor.Methods: Based on NanoBit® technology, a protein complementation assay was developed in which the A1AR is coupled to the large part of the nanoluciferase (LgBiT), whereas its small part (SmBiT) is fused to the N-terminus of β-arrestin 2. Stimulation of A1AR results in the recruitment of β-arrestin 2 and subsequent complementation of a functional nanoluciferase. For comparison, corresponding data on the effect of receptor stimulation on intracellular cAMP levels were collected for some data sets using the GloSensor™ assay.Results: The assay gives highly reproducible results with a very good signal-to-noise ratio. Capadenoson, in contrast to adenosine, CPA, or NECA, shows only partial agonism in this assay with respect to the recruitment of β-arrestin 2, whereas it shows full agonism in the case of the inhibitory effect of A1AR on cAMP production. By using a GRK2 inhibitor, it becomes clear that the recruitment is at least partially dependent on the phosphorylation of the receptor by this kinase. Interestingly, this was also the first time that we demonstrate the A1AR-mediated recruitment of β-arrestin 2 by stimulation with a valerian extract.Conclusion: The presented assay is a useful tool for the quantitative study of A1AR-mediated β-arrestin 2 recruitment. It allows data collection for stimulatory, inhibitory, and modulatory substances and is also suitable for more complex substance mixtures such as valerian extract.
Mapping new pharmacological interventions for cognitive function in Alzheimer’s disease: a systematic review of randomized clinical trials
Authors: Xu Lou Inmaculada , Chen Jiayue , Ali Kamran , Shaikh Abdul Lateef , Chen Qilan 
Published: June 2023

Background and Objective: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, that is, characterized by cognitive decline. To date, there are no effective treatments for AD. Therefore, the objective of this study was to map new perspectives on the effects of pharmacological treatment on cognitive function and the overall psychological state in patients with AD.Methods: Two independent researchers searched for randomized clinical trials (RCTs) exploring new pharmacological approaches related to cognition in Alzheimer’s disease in adults from 2018 to 2023 in PubMed, Web of Science, Scopus, and Cochrane Library databases. A total of 17 RCTs were included in this review.Results: The results show that in recent years, new drugs have been tested in patients with Alzheimer’s disease, including masitinib, methylphenidate, levetiracetam, Jiannao Yizhi, and Huannao Yicong formulas. Most studies have been conducted in populations with mild to moderate Alzheimer’s disease.Conclusion: Although some of the drugs found suggested improvement in cognitive function, the scarcity of available studies highlights the need for further research in this area.Systematic review registration: [www.crd.york.ac.uk/prospero], identifier [CRD42023409986].
The elucidation of the anti-inflammatory mechanism of EMO in rheumatoid arthritis through an integrative approach combining bioinformatics and experimental verification
Authors: Hui Pusheng , Zhou Sicong , Cao Chunhao , Zhao Wenting , Zeng Li , Rong Xiaofeng 
Published: June 2023

Introduction: Emodin (EMO), a natural derivative of the anthraquinone family mainly extracted from rhubarb (Rheum palmatum), has previously been demonstrated to possess superior anti-inflammatory properties from a single target or pathway. In order to explore the underlying mechanism of action of EMO against rheumatoid arthritis (RA), a network pharmacology approach was employed.Methods: A gene expression profile from GSE55457 available from the Gene Expression Omnibus (GEO) database was used to identify the targets of EMO action. Further, single cell RNA sequencing data from GEO database of RA patients (GSE159117) were downloaded and analysed. To further investigate the anti-RA effect of EMO on MH7A cells, the expression of IL-6 and IL-1β were monitored. Finally, RNA-seq analyses were conducted on synovial fibroblasts from EMO-treated.Result: We screened the key targets of EMO against RA using network pharmacology methods, including HMGB1, STAT1, EGR1, NR3C1, EGFR, MAPK14, CASP3, CASP1, IL4, IL13, IKBKB and FN1, and their reliability was verified using ROC curve. Single-cell RNA sequencing data analysis showed that these core target proteins mainly played a role by modulating monocytes. The anti-RA effect of EMO was further verified with MH7A cells, which showed that EMO could block cell differentiation and reduce the expression of IL-6 and IL-1β. WB experiments confirmed that EMO could affect the expression of COX2, HMBG1 and the phosphorylation of p38. Finally, sequencing of synovial fibroblasts from rats treated with EMO showed consistent results with those predicted and verified, further proving the anti-inflammatory effect of EMO.Conclusion: Our research shows that EMO inhibits inflammatory response of rheumatoid arthritis (RA) by targeting HMGB1, STAT1, EGR1, NR3C1, EGFR, MAPK14, CASP3, CASP1, IL4, IL13, IKBKB, FN1 and Monocytes/macrophages.
The effect of confounding variables on the relationship between anthropometric and physiological features in 2000-m rowing ergometer performance
Authors: Podstawski Robert , Borysławski Krzysztof , Alföldi Zoltán , Ferenc Ihász , Wąsik Jacek 
Published: June 2023

Background:Anthropometric and physiological characteristics are often considered as potential variables that are significantly related with motor performance.Aim:The aim of this study was to identify and weigh the key anthropometric and physiological characteristics that are associated with 2000-m rowing ergometer performance in male and female athletes.Methods:The study involved 70 best female and 130 best male rowers from the seven largest Hungarian rowing clubs, classified into one of the following age categories: juniors (36 women and 55 men, age range: 15-16 years), older juniors (26 women and 52 men, age range: 17-18 years), and seniors (8 women and 23 men, age range: over 18 years). Anthropometric and body composition measurements were determined by the bioelectrical impedance method proposed by Weiner and Lourie (1969), and skin fold measurements were conducted to estimate relative body fat content. The countermovement jump test and the 2000-m maximal rowing ergometer test were used for physiological measurements.Results:An increase in skeletal muscle mass was correlated (r= -.39,p&lt;.001) with a significant decrease in rowing time over a distance of 2000 m, whereas a significant increase in rowing time was noted with an increase in sitting height (only in men,r= .33,p&lt;.001), body mass (in women and men:r= .24,p= .013 andr= .31,p= .009), and body fat percentage (r= .26,p&lt; .030). Rowing time was also bound by a significant correlation with maximal force (r= -.79 and -.90,p&lt;.001) and relative maximal power (r= -.54 and -.78,p&lt;.001) in both sexes, with relative peak power in males (r= -.51,p&lt; .001), and with estimated relative maximal aerobic capacity in females (r= -.43,p&lt;.001).Conclusion:Rowing performance over a distance of 2000 m is significantly negatively correlated with the skeletal muscle mass, maximal force, relative maximal power, relative peak power, and estimated relative maximal aerobic capacity.
The relationship between parental mental health, reflective functioning coparenting and social emotional development in 0-3 year old children
Authors: De Palma Mia , Rooney Rosanna , Izett Elizabeth , Mancini Vincent , Kane Robert 
Published: June 2023

IntroductionThe transition to parenthood is a high-risk period for many parents and is an important period for child development. Research has identified that parental mental health, reflective functioning (capacity to consider mental states of oneself and others) and coparenting (capacity to work together well as a parenting team) may be particularly significant predictors of later child outcomes, however these factors have seldom been considered together. The present study therefore aimed to investigate the relationship between these factors and the extent to which they predict child social emotional development.MethodsThree hundred and fifty parents of infants aged 0 to 3 years 11 months were recruited to complete an online Qualtrics questionnaire.ResultsResults indicate that both positive coparenting and parental reflective functioning (Pre-mentalizing and Certainty subscales) were found to significantly predict child development. General reflective functioning (Uncertainty subscale) predicted parental depression and anxiety, however unexpectedly, parental mental health was not a significant predictor of child development, but did predict coparenting. General reflective functioning (Certainty subscale) was also found to predict coparenting, which in turn was found to predict parental reflective functioning. We found an indirect effect of general reflective functioning (Certainty) on child SE development via parental reflective functioning (Pre-mentalizing). We also found an indirect effect of negative coparenting on child development via parental reflective functioning (Pre-mentalizing).DiscussionThe current results support a growing body of research highlighting the important role reflective functioning plays in child development and wellbeing as well as parental mental health and the interparental relationship.
Fine particulate matter air pollution and the mortality of children under five: a multilevel analysis of the Ethiopian Demographic and Health Survey of 2016
Authors: Shiferaw Ashenafie Bereded , Kumie Abera , Tefera Worku 
Published: June 2023

BackgroundEvery year, polluted air is costing the globe 543,000 deaths of children under five. The particulate matter below 2.5 μm diameter (PM2.5) is a part of air pollution that has adverse effects on children’s health. In Ethiopia, the effect of ambient PM2.5 is least explored. This study aimed to assess the association between PM2.5 and under-five mortality in Ethiopia.MethodsThe study used the data from the Ethiopian Demographic Health Surveys conducted in 2016, collected between January 18 and June 27. All children under five who had data on child mortality and location coordinates were included in the study. Exposure to ambient PM2.5 concentration was a satellite-based estimate by the Atmospheric Composition Analysis Group at Washington and Dalhousie University, in the United States and Canada, respectively. Annual mean pollution levels and mortality datasets were matched by children’s geographical location and dates of birth, death, and interview. The relationship between ambient PM2.5 and under-five mortality was determined by a multilevel multivariable logistic regression on R software. The statistical analyses were two-sided at a 95% confidence interval.ResultsThe study addressed 10,452 children with the proportion of under-five mortality being 5.4% (95% CI 5.0–6.8%). The estimated lifetime annual mean exposure of ambient total PM2.5 was 20.1 ± 3.3 μgm−3. A 10-unit increase in the lifetime annual mean ambient total PM2.5 was associated with 2.29 [95% CI 1.44, 3.65] times more odds of under-five mortality after adjusting for other variables.ConclusionChildren under five are exposed to higher levels of ambient PM2.5 concentration, exceeding the limit set by the World Health Organization. Ambient PM2.5 is significantly associated with under-five mortality, adjusting for other variables. Strong measures need to be taken to reduce air pollution.
Climate variability, socio-economic conditions and vulnerability to malaria infections in Mozambique 2016–2018: a spatial temporal analysis
Authors: Armando Chaibo Jose , Rocklöv Joacim , Sidat Mohsin , Tozan Yesim , Mavume Alberto Francisco , Bunker Aditi , Sewes Maquins Odhiambo 
Published: June 2023

BackgroundTemperature, precipitation, relative humidity (RH), and Normalized Different Vegetation Index (NDVI), influence malaria transmission dynamics. However, an understanding of interactions between socioeconomic indicators, environmental factors and malaria incidence can help design interventions to alleviate the high burden of malaria infections on vulnerable populations. Our study thus aimed to investigate the socioeconomic and climatological factors influencing spatial and temporal variability of malaria infections in Mozambique.MethodsWe used monthly malaria cases from 2016 to 2018 at the district level. We developed an hierarchical spatial–temporal model in a Bayesian framework. Monthly malaria cases were assumed to follow a negative binomial distribution. We used integrated nested Laplace approximation (INLA) in R for Bayesian inference and distributed lag nonlinear modeling (DLNM) framework to explore exposure-response relationships between climate variables and risk of malaria infection in Mozambique, while adjusting for socioeconomic factors.ResultsA total of 19,948,295 malaria cases were reported between 2016 and 2018 in Mozambique. Malaria risk increased with higher monthly mean temperatures between 20 and 29°C, at mean temperature of 25°C, the risk of malaria was 3.45 times higher (RR 3.45 [95%CI: 2.37–5.03]). Malaria risk was greatest for NDVI above 0.22. The risk of malaria was 1.34 times higher (1.34 [1.01–1.79]) at monthly RH of 55%. Malaria risk reduced by 26.1%, for total monthly precipitation of 480 mm (0.739 [95%CI: 0.61–0.90]) at lag 2 months, while for lower total monthly precipitation of 10 mm, the risk of malaria was 1.87 times higher (1.87 [1.30–2.69]). After adjusting for climate variables, having lower level of education significantly increased malaria risk (1.034 [1.014–1.054]) and having electricity (0.979 [0.967–0.992]) and sharing toilet facilities (0.957 [0.924–0.991]) significantly reduced malaria risk.ConclusionOur current study identified lag patterns and association between climate variables and malaria incidence in Mozambique. Extremes in climate variables were associated with an increased risk of malaria transmission, peaks in transmission were varied. Our findings provide insights for designing early warning, prevention, and control strategies to minimize seasonal malaria surges and associated infections in Mozambique a region where Malaria causes substantial burden from illness and deaths.
Association of urinary phthalate metabolites with all-cause and cardiovascular disease mortality among adults with diabetes mellitus: National Health and Nutrition Examination Survey 2005–2014
Authors: Wang Zhihong , Deng Yao , Gao Sikang , Lin Zefang , Zheng Zhixiong , Fang Qin , Zhan Meixiao , Sun Taoping , Huang Guomin , Geng Xuyang 
Published: June 2023

BackgroundThe study regarding phthalate metabolites and mortality among diabetes mellitus (DM) is limited. We aimed to examine the association of urinary phthalate metabolites with all-cause and cardiovascular disease (CVD) mortality among adults with DM.MethodsThis study included 8,931 adults from the National Health and Nutrition Examination Survey (NHANES) from 2005–2006 to 2013–2014. Mortality data were linked to National Death Index public access files through December 31, 2015. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidences (CIs) for mortality.ResultsWe identified 1,603 adults with DM [mean ± SE age, 47.08 ± 0.30 years; 50.5% (833) were men]. Mono-(carboxynonyl) phthalate (MCNP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP), and the sum of Di (2-ethylhexyl) phthalate (DEHP) metabolites (∑DEHP) were positively associated with DM (MCNP: OR = 1.53, 95%CI = 1.16–2.01; MECPP: OR = 1.17, 95% CI = 1.03–1.32; ∑DEHP: OR = 1.14, 95% CI = 1.00–1.29). Among DM patients, mono-(3-carboxypropyl) phthalate (MCPP) was associated with a 34% (HR 1.34, 95% CI 1.12–1.61) increased risk of all-cause mortality while the HRs (95%CI) of CVD mortality were 2.02 (1.13–3.64) for MCPP, 2.17 (1.26–3.75) for mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), 2.47 (1.43–4.28) for mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), 2.65 (1.51–4.63) for MECPP, and 2.56 (1.46–4.46) for ∑DEHP, respectively.ConclusionThis study is an academic exploration of the association between urinary phthalate metabolites and mortality among adults with DM, suggesting that exposure to phthalates might be associated with an increased risk of all-cause and CVD mortality in DM. These findings suggest that patients with DM should carefully use plastics products.
Identification of status quo and association rules for chronic comorbidity among Chinese middle-aged and older adults rural residents
Authors: Yu Zijing , Chen Yuquan , Xia Qianhang , Qu Qingru , Dai Tao 
Published: June 2023

BackgroundChronic comorbidity has become a major challenge in chronic disease prevention and control. This issue is particularly pronounced in rural areas of developing countries, where the prevalence of chronic disease comorbidity is high, especially among middle-aged and older adults populations. However, the health status of middle-aged and older adults individuals in rural areas of China has received inadequate attention. Therefore, it is crucial to investigate the correlation among chronic diseases to establish a reference basis for adjusting health policies aimed at promoting the prevention and management of chronic diseases among middle-aged and older adults individuals.MethodsThis study selected 2,262 middle-aged and older adults residents aged 50 years or older in Shangang Village, Jiangsu Province, China, as the study population. To analyze the chronic comorbidity of middle-aged and older adults residents with different characteristics, we used the χ2 test with SPSS statistical software. Data analysis was conducted using the Apriori algorithm of Python software, set to mine the strong association rules of positive correlation between chronic disease comorbidities of middle-aged and older adults residents.ResultsThe prevalence of chronic comorbidity was 56.6%. The chronic disease comorbidity group with the highest prevalence rate was the lumbar osteopenia + hypertension group. There were significant differences in the prevalence of chronic disease comorbidity among middle-aged and older adults residents in terms of gender, BMI, and chronic disease management. The Apriori algorithm was used to screen 15 association rules for the whole population, 11 for genders, and 15 for age groups. According to the order of support, the most common association rules of comorbidity of three chronic diseases were: {lumbar osteopenia} → {hypertension} (support: 29.22%, confidence: 58.44%), {dyslipidemia} → {hypertension} (support: 19.14%, confidence: 65.91%) and {fatty liver} → {hypertension} (support: 17.82%, confidence: 64.17%).ConclusionThe prevalence of chronic comorbidity among middle-aged and older adults rural residents in China is relatively high. We identified many association rules among chronic diseases, dyslipidemia is mostly the antecedent, and hypertension is primarily the result. In particular, the majority of comorbidity aggregation patterns consisted of hypertension and dyslipidemia. By implementing scientifically-proven prevention and control strategies, the development of healthy aging can be promoted.
In Vitro Stability of the Biological Activity of Voriconazole against Acanthamoeba castellanii
Authors: Rodrigues Barbara Czerniak , Büchele Maria Luiza Carneiro , de Camargo Carolina de Jesus , Filippin-Monteiro Fabíola Branco , Caumo Karin Silva 
Published: June 2023

Acanthamoeba keratitis (AK) is a rare cornea disease caused by species of the Acanthamoeba genus. The antifungal voriconazole blocks the ergosterol synthesis in the protozoan membrane and is active against the cysts and trophozoites of Acanthamoeba spp. Due to the low stability of voriconazole, its options for eye drops are scarce. This study aimed to investigate the stability of the biological activity of voriconazole against two strains of Acanthamoeba castellanii and one clinical isolate from a patient with AK. To evaluate the stability of the biological activity of voriconazole, strains of A. castellanii (ATCC 50492) were exposed to different periods and voriconazole concentrations stored at 4 °C for 7, 15, and 30 days. The cytotoxicity assays were performed using SIRC (ATCC CCL-60™) cell line. The results indicated the amoebicidal effect of voriconazole against Acanthamoeba spp. within 24 h and 48 h of exposure, and the voriconazole solution was stable and retained antiamoebic activity when stored at 4 °C for up to 30 days. In the cytotoxicity test, the result demonstrated low cytotoxicity of the drug to the corneal rabbit cell line. However, there is a need to carry out further synergistic effects with other antiamoebic drugs and then in vivo experiments in the AK animal model.