bluuebunny/crossref_metadata_2025_split huggingface dataset:
YIV-818-A: a novel therapeutic agent in prostate cancer management through androgen receptor downregulation, glucocorticoid receptor inhibition, epigenetic regulation, and enhancement of apalutamide, darolutamide, and enzalutamide efficacy
Authors: Lam Wing , Arammash Mohammad , Cai Wei , Guan Fulan , Jiang Zaoli , Liu Shwu-Huey , Cheng Peikwen , Cheng Yung-Chi 
Published: October 2023

Introduction: Prostate cancer is the second leading cause of cancer death among men in the United States. Castration-Resistant Prostate Cancer (CRPC) often develops resistance to androgen deprivation therapy. Resistance in CRPC is often driven by AR variants and glucocorticoid receptor (GR). Thus, drugs that target both could be vital in overcoming resistance.Methods: Utilizing the STAR Drug Discovery Platform, three hundred medicinal plant extracts were examined across 25 signaling pathways to identify potential drug candidates. Effects of the botanical drug YIV-818-A, derived from optimized water extracts of Rubia cordifolia (R.C.), on Dihydrotestosterone (DHT) or Dexamethasone (DEX) induced luciferase activity were assessed in 22RV1 cells harboring the ARE luciferase reporter. Furthermore, the key active compounds in YIV-818-A were identified through activity guided purification. The inhibitory effects of YIV-818-A, RA-V, and RA-VII on AR and GR activities, their impact on AR target genes, and their roles in modifying epigenetic status were investigated. Finally, the synergistic effects of these compounds with established CRPC drugs were evaluated both in vitro and in vivo.Results: YIV-818-A was found to effectively inhibit DHT or DEX induced luciferase activity in 22RV1 cells. Deoxybouvardin (RA-V) was identified as the key active compound responsible for inhibiting AR and GR activities. Both YIV-818-A and RA-V, along with RA-VII, effectively downregulated AR and AR-V proteins through inhibiting protein synthesis, impacted the expression of AR target genes, and modified the epigenetic status by reducing levels of Bromodomain and Extra-Terminal proteins (Brd2/Brd4) and H3K27Ac. Furthermore, these compounds exhibited synergistic effects with apalutamide, darolutamide, or enzalutamide, and suppressed AR mediated luciferase activity of 22RV1 cells. Co-administration of YIV-818-A and enzalutamide led to a significant reduction of 22RV1 tumor growth in vivo. Different sources of R.C. had variable levels of RA-V, correlating with their potency in AR inhibition.Discussion: YIV-818-A, RA-V, and RA-VII show considerable promise in addressing drug resistance in CRPC by targeting both AR protein and GR function, along with modulation of vital epigenetic markers. Given the established safety profile of YIV-818-A, these findings suggest its potential as a chemopreventive agent and a robust anti-prostate cancer drug.
Beneficial effects of ginkgetin on improving nonalcoholic steatohepatitis characterized by bulk and single-cell RNA sequencing analysis
Authors: Wang Chaoyang , Bai Yaowei , Li Tongqiang , Liu Jiacheng , Wang Yingliang , Ju Shuguang , Yao Wei , Xiong Bin , Zhou Guofeng 
Published: October 2023

Background and aims: Nonalcoholic steatohepatitis (NASH) has become one of the major causes of cirrhosis and liver failure. However, there are currently no approved medications for managing NASH. Our study was designed to assess the effects of ginkgetin on NASH and the involved mechanisms.Methods: We constructed a mouse model of NASH by high-fat diet for 24 weeks. The effects of ginkgetin on NASH were evaluated by histological study, Western blot, and biochemical analysis. RNA Sequencing (RNA-Seq) analysis was used to investigate the alteration in gene expression and signaling pathways at bulk and single-cell levels.Results: Administration of ginkgetin resulted in a marked improvement in hepatic lipid accumulation, inflammation, and fibrosis in the NASH model. And these results were supported by bulk RNA-Seq analysis, in which the related signaling pathways and gene expression were markedly downregulated. Furthermore, single-cell RNA-Seq (scRNA-Seq) analysis revealed that the effects of ginkgetin on NASH were associated with the reprogramming of macrophages, hepatic stellate cells, and endothelial cells. Especially, ginkgetin induced a marked decrease in macrophages and a shift from pro-inflammatory to anti-inflammatory phenotype in NASH mice. And the NASH-associated macrophages (NAMs), which emerge during NASH, were also significantly downregulated by ginkgetin.Conclusion: Ginkgetin exhibits beneficial effects on improving NASH, supported by bulk and single-cell RNA-Seq. Our study may promote pharmacological therapy for NASH and raise the existent understanding of NASH.
Machine learning approach to evaluate TdP risk of drugs using cardiac electrophysiological model including inter-individual variability
Authors: Fuadah Yunendah Nur , Qauli Ali Ikhsanul , Marcellinus Aroli , Pramudito Muhammad Adnan , Lim Ki Moo 
Published: October 2023

Introduction: Predicting ventricular arrhythmia Torsade de Pointes (TdP) caused by drug-induced cardiotoxicity is essential in drug development. Several studies used single biomarkers such as qNet and Repolarization Abnormality (RA) in a single cardiac cell model to evaluate TdP risk. However, a single biomarker may not encompass the full range of factors contributing to TdP risk, leading to divergent TdP risk prediction outcomes, mainly when evaluated using unseen data. We addressed this issue by utilizing multi-in silico features from a population of human ventricular cell models that could capture a representation of the underlying mechanisms contributing to TdP risk to provide a more reliable assessment of drug-induced cardiotoxicity.Method: We generated a virtual population of human ventricular cell models using a modified O’Hara-Rudy model, allowing inter-individual variation. IC50 and Hill coefficients from 67 drugs were used as input to simulate drug effects on cardiac cells. Fourteen features (dVmdtrepol, dVmdtmax, Vmpeak, Vmresting, APDtri, APD90, APD50, Capeak, Cadiastole, Catri, CaD90, CaD50, qNet, qInward) could be generated from the simulation and used as input to several machine learning models, including k-nearest neighbor (KNN), Random Forest (RF), XGBoost, and Artificial Neural Networks (ANN). Optimization of the machine learning model was performed using a grid search to select the best parameter of the proposed model. We applied five-fold cross-validation while training the model with 42 drugs and evaluated the model’s performance with test data from 25 drugs.Result: The proposed ANN model showed the highest performance in predicting the TdP risk of drugs by providing an accuracy of 0.923 (0.908–0.937), sensitivity of 0.926 (0.909–0.942), specificity of 0.921 (0.906–0.935), and AUC score of 0.964 (0.954–0.975).Discussion and conclusion: According to the performance results, combining the electrophysiological model including inter-individual variation and optimization of machine learning showed good generalization ability when evaluated using the unseen dataset and produced a reliable drug-induced TdP risk prediction system.
Importance of controlling mesocotyl elongation in the development of rice seedlings intended for mechanical transplantation
Authors: Jia Yuanli , Wang Tao , Zhou Gaozi , Tang Lei , Yue Xueping , Liu Xinrui , Cao Tao , Yang Juan , Tao Youfeng , Deng Fei , Zhou Wei , Ren Wanjun , Chen Yong 
Published: October 2023

The mesocotyl facilities the emergence of deep-sown rice. However, the effects of mesocotyl elongation on mechanically transplanted rice seedlings remain unclear. In this study, the indica three-line hybrid rice Chuanyou 6709 (CY6709) and the indica conventional rice Guichao II (GCII) were selected as experimental materials. The seedlings were grouped based on mesocotyl lengths of 1.0 and 2.0 cm (M1 and M2, respectively), and seedlings without mesocotyl elongation were used as a control (M0). Seedling morphology, root morphology and physiology, and dynamic changes in soluble sugar and protein, malondialdehyde (MDA), and antioxidant enzyme activity in the mesocotyl were evaluated. The results showed that the elongation of mesocotyl is not conducive to improving the quality of mechanically transplanted seedlings, resulting in weak seedlings and poor root coiling force. The mesocotyl lengths of the seedlings showed a single peak with increasing seedling age, which gradually disappeared. The longer the mesocotyls, the slower their senescence. The MDA content of M2 was significantly lower than that of M1, and the activities of soluble sugar, soluble protein, and antioxidant enzymes of M2 were higher than those of M1, implying that seedlings with longer mesocotyls yielded lower-quality seedlings, reducing their suitability for mechanized transplantation. Compared with those of M0, the root-shoot ratio, stem base width, leaf age, leaf area, white root number, root coiling force, root length, root surface area, and root volume of M1 and M2 were reduced. Therefore, in the raising of rice seedlings, excessive elongation of the rice mesocotyl is not conducive to optimum root growth and development of aboveground structures for seedlings that are suitable for mechanized transplantation. Controlling the mesocotyl elongation can facilitate the cultivation of high-quality mechanically transplanted seedlings.
Comparative analysis of KNOX genes and their expression patterns under various treatments in Dendrobium huoshanense
Authors: Li Guohui , Manzoor Muhammad Aamir , Wang Guoyu , Chen Cunwu , Song Cheng 
Published: October 2023

IntroductionKNOX plays a pivotal role in governing plant growth, development, and responses to diverse abiotic and biotic stresses. However, information on the relationship between the KNOX gene family and expression levels under different treatments in Dendrobium is still limited.MethodsTo address this problem, we first used bioinformatics methods and revealed the presence of 19 KNOX genes distributed among 13 chromosomes in the Dendrobium huoshanense genome. Through an analysis of phylogenetic relationships, these genes were classified into three distinct clades: class I, class II, and class M. Our investigation included promoter analysis, revealing various cis-acting elements associated with hormones, growth and development, and abiotic stress responses. Additionally, qRT-PCR experiments were conducted to assess the expression patterns of DhKNOX genes under different treatments, including ABA, MeJA, SA, and drought.ResultsThe results demonstrated differential expression of DhKNOX genes in response to these treatments, thereby highlighting their potential roles in stress adaptation.DiscussionOverall, our results contribute important insights for further investigations into the functional characterization of the Dendrobium KNOX gene family, shedding light on their roles in plant development and stress responses.
Identification of the role of immune-related genes in the diagnosis of bipolar disorder with metabolic syndrome through machine learning and comprehensive bioinformatics analysis
Authors: Shen Jing , Feng Yu , Lu Minyan , He Jin , Yang Huifeng 
Published: October 2023

BackgroundBipolar disorder and metabolic syndrome are both associated with the expression of immune disorders. The current study aims to find the effective diagnostic candidate genes for bipolar affective disorder with metabolic syndrome.MethodsA validation data set of bipolar disorder and metabolic syndrome was provided by the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were found utilizing the Limma package, followed by weighted gene co-expression network analysis (WGCNA). Further analyses were performed to identify the key immune-related center genes through function enrichment analysis, followed by machine learning-based techniques for the construction of protein–protein interaction (PPI) network and identification of the Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest (RF). The receiver operating characteristic (ROC) curve was plotted to diagnose bipolar affective disorder with metabolic syndrome. To investigate the immune cell imbalance in bipolar disorder, the infiltration of the immune cells was developed.ResultsThere were 2,289 DEGs in bipolar disorder, and 691 module genes in metabolic syndrome were identified. The DEGs of bipolar disorder and metabolic syndrome module genes crossed into 129 genes, so a total of 5 candidate genes were finally selected through machine learning. The ROC curve results-based assessment of the diagnostic value was done. These results suggest that these candidate genes have high diagnostic value.ConclusionPotential candidate genes for bipolar disorder with metabolic syndrome were found in 5 candidate genes (AP1G2, C1orf54, DMAC2L, RABEPK and ZFAND5), all of which have diagnostic significance.
The impact of exercise on mental health during the COVID-19 pandemic: a systematic review and meta-analysis
Authors: Wang Chaochao , Tian Zuguo , Luo Qiaoyou 
Published: October 2023

IntroductionAmidst the COVID-19 pandemic, there has been a global surge in mental health challenges. This study (PROSPERO CRD42023443860) aimed to investigate the impact of exercise on individuals’ mental health through systematic evaluation and meta-analysis to develop a scientific exercise program.MethodsWe systematically searched the literature up to August 2023 using PubMed, Web of Science, and SCOPUS. The Cochrane Risk Assessment Tool gaged the methodological quality of the included literature.ResultsAmong the initially identified 10,343 search records, 12 studies were deemed to meet the criteria for systematic review and meta-analysis. Exercise significantly improved anxiety (SMD -0.81, 95% CI -1.10 to −0.52, p  &lt; 0.00001), depression (−1.02, 95% CI -1.42 to −0.62, p  = 0.0001), stress (−1.05, 95% CI -1.33 to −0.78, p  &lt; 0.00001), and quality of life (1.11, 95% CI 0.81 to 1.41, p  &lt; 0.00001). Subgroup analyzes indicated that a single exercise session lasting 30–40 min had the most pronounced effect on reducing anxiety (−1.29, 95% CI -1.12 to −0.86, p  &lt; 0.00001) and depression (−1.76, 95% CI -2.24 to −1.28, p  &lt; 0.00001). Similarly, an exercise frequency of 3–5 times per week yielded the greatest benefits for anxiety (−1.31, 95% CI -2.15 to −0.46, p  &lt; 0.00001) and depression (−1.27, 95% CI -2.11 to −0.41, p  = 0.0003). Notably, exercise exhibited its most significant impact on depression improvement in the 40–64 age group (−1.32, 95% CI -1.78 to −0.86, p  &lt; 0.00001). Moreover, exercise notably enhanced anxiety levels among individuals in middle and upper-income brackets (−0.99, 95% CI -1.11 to −0.87, p  &lt; 0.00001).ConclusionExercise alleviated anxiety disorders, depression, stress levels, and quality of life during the COVID-19 pandemic. The most significant impact on anxiety and depression improvement is achieved by engaging in 30–40 min of exercise sessions, 3–5 times per week.
Genome-wide association study of mammary gland tumors in Maltese dogs
Authors: Kim Keon , Song Jung Eun , Joo Jae Beom , Park Hyeon A , Choi Chang Hyeon , Je Chang Yun , Kim Ock Kyu , Park Sin Wook , Do Yoon Jung , Hur Tai-Young , Park Sang-Ik , Lee Chang-Min 
Published: October 2023

BackgroundA genome-wide association study (GWAS) is a valuable tool for investigating genetic and phenotypic variation in many diseases.ObjectiveThe objective of this study was to identify variations in the genomes of Maltese dogs that are associated with the mammary gland tumor (MGT) phenotype and to assess the association between each biological condition and MGT phenotype in Maltese dogs.MethodsDNA was extracted from 22 tumor samples and 11 whole blood samples from dogs with MGTs. Genome-wide single-nucleotide polymorphism (SNP) genotyping was performed, and the top 20 SNPs associated with various conditions and genetic variations were mapped to their corresponding gene locations.ResultsThe genotyping process successfully identified 173,662 loci, with an overall genotype completion rate of 99.92%. Through the quality control analysis, 46,912 of these SNPs were excluded. Allelic tests were conducted to generate Manhattan plots, which showed several significant SNPs associated with MGT phenotype in intergenic region. The most prominent SNP, located within a region associated with transcription and linked to the malignancy grade of MGT, was identified on chromosome 5 (p = 0.00001) though there may be lack of statistical significance. Other SNPs were also found in several genes associated with oncogenesis, including TNFSF18, WDR3, ASIC5, STAR, and IL1RAP.ConclusionTo our knowledge, this is the first GWAS to analyze the genetic predisposition to MGT in Maltese dogs. Despite the limited number of cases, these analyzed data could provide the basis for further research on the genetic predisposition to MGTs in Maltese dogs.
New Supersonic Nozzle Test Rig Used to Generate Condensing Flow Test Data According to Barschdorff
Authors: Maqueo Martínez Manuel Ernesto , Schippling Stefan , Schatz Markus , Vogt Damian M. 
Published: October 2023

Considerable progress has been achieved in recent decades in understanding the phenomena related to the onset of condensation in steam flows, both experimentally and especially numerically. Nevertheless, there is still a certain disagreement between the different numerical models used. Unfortunately, the available experimental validation data are not sufficiently detailed to allow for proper validation of computational fluid dynamics (CFD) simulations. Therefore, this paper presents new experimental data for condensing steam flows, acquired in a supersonic nozzle according to Barschdorff, at the Institute of Thermal Turbomachinery Laboratory (ITSM) at the University of Stuttgart. A steady inlet pressure of approximately 784 mbar was set for three inlet temperatures down to 100.2 ∘C. Condensation onset is accurately captured across the nozzle, using down to 1 mm spatial resolution for both pneumatic and light spectra measurements. CFD simulations were performed using the commercial solver ANSYS CFX. The droplet diameters are numerically overestimated by approximately a factor of 1.5. Disagreement has been found between original Barschdorff’s experiments and measurements at ITSM. However, there is a good agreement in terms of the pressure distribution along the nozzle axis between experimental and numerical results. The reproducibility of the results is excellent.
Post-hospitalisation asthma management in primary care: a retrospective cohort study
Authors: Punyadasa Dhanusha , Simms-Williams Nikita , Adderley Nicola J , Thayakaran Rasiah , Mansur Adel H , Nirantharakumar Krishnarajah , Nagakumar Prasad , Haroon Shamil 
Published: October 2023

BackgroundClinical guidelines recommend that patients admitted to hospital for asthma attacks are reviewed in primary care following hospital discharge.AimTo evaluate asthma management in primary care following a hospital admission for asthma and its associations with patient characteristics.Design and settingA retrospective cohort study using English primary care data from the Clinical Practice Research Datalink Aurum database and linked Hospital Episode Statistics Admitted Patient Care data.MethodPatients with asthma aged ≥5 years who had at least one asthma-related hospital admission from 1 January 2017 to 31 December 2019 were included. The primary outcome was a composite of any of the following delivered in primary care within 28 days from hospital discharge: asthma review, asthma management plan, asthma medication prescriptions, demonstration of inhaler technique, or smoking cessation counselling. The association between patient characteristics and delivery of clinical care was assessed using logistic regression.ResultsThe study included 17 457 patients. A total of 10 515 (60.2%) patients received the primary outcome within 28 days of hospital discharge. There were 2311 (13.2%) who received an asthma review, 1459 (8.4%) an asthma management plan, 9996 (57.3%) an asthma medication, 1500 (8.6%) a demonstration of inhaler technique, and 52 (1.2% of smokers) had smoking cessation counselling. Patients from Black ethnic minority groups received less of this care (27%– 54% lower odds, depending on age). However, short-acting bronchodilator prescriptions in the previous year were associated with an increased likelihood of the primary outcome.ConclusionA significant proportion of patients do not receive timely follow-up in primary care following asthma-related admissions to hospital, particularly among Black ethnic minority groups.
Aspects de l’internationalisation du capital dans les pays à économie de marché
Authors: Lacroix Anne , Mollard Amédée 
Published: October 2023

Le processus d'internationalisation en Europe occidentale se traduit tout d'abord par une concentration géographique du commerce extérieur de produits agro-alimenaires. Sous l'influence de la protection communautaire, cette concentration est devenue très forte entre les pays membres de la CEE dont les secteurs agro-alimentaires sont de plus en plus interdépendants. Mais la polarisation des échanges ouest-européens touche aussi des pays comme le Portugal ou la Turquie dont les relations commerciales avec la CEE s'accroissent.
L'intensité de ces échanges extérieurs reflète en réalité la vigueur du processus d'internationalisation au niveau de la production agro-alimentaire elle-même, sous l'influence grandissante des firmes multinationales situées en amont et en aval de l'agriculture. Dans tous les pays, ces firmes occupent une place de plus en plus grande sur les marchés des moyens de production destinés à l'agriculture et sur ceux des produits alimentaires transformés. De ce fait, les pays oit ces technologies sont mises au point, produites et exportées, occupent une position dominante par rapport aux pays qui doivent les acheter.
Firmes multinationales et politiques étatiques : deux éléments-clé de l’internationalisation agro-alimentaire en Europe occidentale
Authors: Lacroix Anne , Mollard Amédée 
Published: October 2023

C'est dans les pays d'Europe occidentale où l'intégration économique de l'agriculture aux industries d'amont et d'aval est forte et où ces industries sont elles-mêmes de grande dimension et concentrées que le processus d'internationalisation du secteur agro-alimentaire prend le plus d'ampleur : il affecte alors à la fois les conditions de production et d'échange. Dans les pays moins industrialisés, même si les firmes multinationales sont fortement implantées, la moindre intégration de l’agriculture aux industries alimentaires diminue l'impact du processus d'internationalisation sur l'agriculture.
Dans tous les pays, l'intervention de l'Etat, grâce à sa politique des prix et des marchés, à son action sur les structures du secteur agro-alimentaire et à ses aides financières, appuie et renforce le processus d'internationalisation. Cependant, l'impact des interventions étatiques est plus fort dans les pays de la CEE où la politique agricole commune prend le relais des politiques agricoles nationales.
Conséquences et perspectives du processus d'internationalisation du secteur agro-alimentaire en Europe occidentale
Authors: Mollard Amédée 
Published: October 2023

Le constat, pays par pays, des effets différenciés du processus d’internationalisation sur les différents secteurs agro-alimentaires, nous conduit à hiérarchiser les six pays analysés en deux groupes :
— d'un côté, le Royaume-Uni, la R.F.A. et la France où les effets bénéfiques du processus d'internationalisation paraissent l'emporter sur les inconvénients ;
— de l'autre, le Portugal et la Turquie, et souvent l'Italie, où les effets négatifs l'emportent.
Les facteurs de différenciations tiennent au niveau d'industrialisation, aux problèmes monétaires et à l'inégale maîtrise des technologies .
L'avenir du processus d'internationalisation en Europe occidentale paraît conditionné par des facteurs à la fois politiques et économiques. Ceux-ci détermineront sans doute une extension géographique de ce processus en Europe et en direction des pays en voie de développement et peut-être son approfondissement, à la faveur de la crise économique actuelle.