bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma urea cycle metabolite levels and the risk of moyamoya disease
Authors: Yu Xiaofan , Ge Peicong , Zhai Yuanren , Liu Wei , Zhang Qian , Ye Xun , Liu Xingju , Wang Rong , Zhang Yan , Zhao Jizong , Zhang Dong 
Published: July 2023

Background and purposeUrea cycle metabolites are expected to be the biomarkers for cerebrovascular diseases. However, the effects of circulating urea cycle metabolites on the risk of MMD and its subcategories remain unclear. The aim of this study was to prospectively investigate the association between plasma urea cycle metabolites and the risk of MMD and its subcategories.MethodsWe measured plasma urea cycle metabolite levels for 360 adult MMD patients and 89 matched healthy controls. Clinical and laboratory characteristics were obtained from the medical record. The study was conducted from July 2020 to December 2021.ResultsAfter multivariate adjustment, the risk of MMD increased with each increment in ornithine level (per natural log [ornithine] increment: OR, 3.893; 95% CI, 1.366–11.090). The risk of MMD decreased with each increment in arginine level (per natural log [arginine] increment: OR, 0.109; 95% CI, 0.028–0.427), urea level (per natural log [urea] increment: OR, 0.261; 95% CI, 0.072–0.940), and global arginine bioavailability ratio (GABR) level (per natural log [GABR] increment: OR, 0.189; 95% CI, 0.074–0.484). The addition of plasma arginine (integrated discrimination improvement: 1.76%, p = 0.021) or GABR (integrated discrimination improvement: 1.76%, p = 0.004) to conventional risk factors significantly improved the risk reclassification for MMD.ConclusionPlasma ornithine levels are positively associated with the risk of MMD. By contrast, the levels of arginine, urea, and GABR are inversely related to the risk of MMD. Plasma urea cycle metabolites might be potential biomarkers for the risk of MMD.
Global ginseng trade networks: structural characteristics and influencing factors
Authors: Fang Yue , Tang Mengxue , Wei Hua , Feng Zhipei , Yu Nianjun 
Published: July 2023

Background: Ginseng is a rare and highly valued Chinese materia medica with a rich trading history and has a wide range of application, including medicine, food, healthcare, and daily chemical production. However, the global trade of ginseng exhibits diverse features and uneven development across different countries and regions. Surprisingly, the intricate network relationship and the underlying characteristics and influencing factors of ginseng trade networks remain unexplored.Methods: This study analyzed ginseng trade data obtained from the UN-Comtrade database and used social network analysis to construct global ginseng trade networks. To elucidate the structural characteristics, we analyzed the indicators of the overall network structure and node attributes. Core-periphery analysis is used to examine the evolutionary patterns within the global ginseng trade networks. Furthermore, we apply the quadratic assignment procedure to investigate the impact and relevance of spatial proximity, cultural differences, economic indicators, population size, technological similarity, and institutional distance.Results: The findings reveal that the global ginseng trade networks exhibit typical small-world and scale-free properties, as well as a core-periphery structure. Several core countries, including China, South Korea, Germany, and the United States, exert significant control over both trade volume and trade partners. South Korea and China initially occupied central positions in the export market due to their resource endowments, their prominence has gradually diminished with the ascendancy of Germany and the United States. According to the core-periphery analysis, the ginseng trade has shown a gradual concentration within specific trade groups comprising core and semi-periphery countries, most of which are along the “Belt and Road” religion. We also found that geographic distance and GDP per capita exert negative effects on ginseng trade, while factors such as land adjacency, technology and economic gap, population size, and institution similarity play significant positive roles.Conclusion: The global ginseng trade has experienced increasing concentration and close linkage among a limited numbers of participants. It is crucial to pay close attention to the relationship between ginseng industry development and resource conservation. Strategies such as expanding trade channels, implementing trade substitution measures, and optimizing the quality and standards of ginseng products can effectively enhance trade security.
Effects of bergapten on the pharmacokinetics of macitentan in rats both in vitro and in vivo
Authors: Xu Jia , Zhou Quan , Hou Pengjiao , Wang Yu , Geng Peiwu , Lu Zebei , Zhou Yunfang , Dai Dapeng , Wang Shuanghu 
Published: July 2023

Macitentan was approved by the United States Food and Drug Administration (FDA) in 2013 for the treatment of pulmonary arterial hypertension (PAH). Bergapten is a furanocoumarin that is abundant in Umbelliferae and Rutaceae plants and is widely used in many Chinese medicine prescriptions. Considering the possible combination of these two compounds, this study is aimed to investigate the effects of bergapten on the pharmacokinetics of macitentan both in vitro and in vivo. Rat liver microsomes (RLMs), human liver microsomes (HLMs), and recombinant human CYP3A4 (rCYP3A4) were used to investigate the inhibitory effects and mechanisms of bergapten on macitentan in vitro. In addition, pharmacokinetic parameters were also studied in vivo. Rats were randomly divided into two groups (six rats per group), with or without bergapten (10 mg/kg), and pretreated for 7 days. An oral dose of 20 mg/kg macitentan was administered to each group 30 min after bergapten or 0.5% CMC-Na administration on day 7. Blood was collected from the tail veins, and the plasma concentrations of macitentan and its metabolites were assessed by ultra-performance liquid chromatography - tandem mass spectrometer (UPLC-MS/MS). Finally, we analyzed the binding force of the enzyme and two small ligands by in silico molecular docking to verify the inhibitory effects of bergapten on macitentan. The in vitro results revealed that the IC50 values for RLMs, HLMs, and rCYP3A4 were 3.84, 17.82 and 12.81 μM, respectively. In vivo pharmacokinetic experiments showed that the AUC(0-t), AUC(0-∞), and Cmax of macitentan in the experimental group (20,263.67 μg/L*h, 20,378.31 μg/L*h and 2,999.69 μg/L, respectively) increased significantly compared with the control group (7,873.97 μg/L*h, 7,897.83 μg/L*h and 1,339.44 μg/L, respectively), while the CLz/F (1.07 L/h/kg) of macitentan and the metabolite-parent ratio (MR) displayed a significant decrease. Bergapten competitively inhibited macitentan metabolism in vitro and altered its pharmacokinetic characteristics in vivo. Further molecular docking analysis was also consistent with the experimental results. This study provides a reference for the combined use of bergapten and macitentan in clinical practice.
Efficacy and safety of Qiangli Dingxuan tablet combined with amlodipine besylate for essential hypertension: a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial
Authors: Lin Jianguo , Wang Qingqing , Zhong Dongsheng , Zhang Jinju , Yuan Tianhui , Wu Hui , Li Bin , Li Shuangdi , Xie Xiaoliu , An Dongqing , Deng Yue , Xian Shaoxiang , Xiong Xingjiang , Yao Kuiwu 
Published: July 2023

Background: Hypertension, a major cardiovascular risk factor, severely impacts patients’ quality of life. Qiangli Dingxuan tablet (QDT) is a formally approved Chinese patent medicine, which has been widely used as an adjunctive treatment for hypertension. This study aimed to investigate the antihypertensive efficacy and safety of QDT combined with amlodipine besylate in patients with essential hypertension.Methods: In this randomized, double-blind, placebo-controlled, parallel-group, multicenter trial conducted in China, patients diagnosed with grade 1 to 2 essential hypertension were randomly assigned in a 1:1 to the treatment of QDT or placebo for 12 weeks, alongside their ongoing treatment with amlodipine besylate. The primary outcome was the change in office blood pressure (BP) from baseline to 12 weeks. In addition, safety analysis included the assessment of vital signs and laboratory values.Results: At baseline, 269 patients were randomly assigned to the QDT group (n = 133) or the placebo group (n = 136), and there were no significant differences in baseline characteristics between the two groups. The primary outcome based on the full analysis set from baseline to 12 weeks showed that the mean difference in the change of office systolic BP reduction between the two groups was 6.86 mmHg (95%CI, 4.84 to 8.88, p &lt; 0.0001), for office diastolic BP, the mean difference in the change of office diastolic BP reduction between the two groups was 4.64 mmHg (95%CI, 3.10 to 6.18, p &lt; 0.0001). In addition, traditional Chinese medicine symptom scores were significantly decreased in the QDT group compared with the placebo group. No severe adverse events attributable to QDT were reported.Conclusion: The combination of QDT and amlodipine besylate demonstrates superior efficacy compared to amlodipine besylate monotherapy in the management of essential hypertension. QDT shows potential as an adjunctive treatment for essential hypertension. However, further rigorous clinical trials are warranted to validate these findings.Clinical Trial Registration: [https://clinicaltrials.gov/study/NCT05521282?cond=NCT05521282&amp;rank=1]; Identifier: [NCT05521282]
Noiseless Variable-Pressure Neck Chamber Device to Assess the Carotid Baroreflex Function
Authors: Pinheiro Alessandro , Vianna Lauro C. , Carmo Jake C. 
Published: July 2023

Background: The blood pressure responses to baroreflex perturbations can be assessed only using the variable-pressure neck chamber technique. However, the application of this approach in hospital environments is limited owing to the loud noise emitted during its operation. This study was aimed at developing a noiseless neck suction chamber device (NCD) that could stimulate the baroreceptors located in the carotid sinus in humans.Methods: A non-invasive device was developed to pressurize the carotid arteries externally. A microcontroller with a computer interface and neck chamber (3D-printed) was used. The anatomical neck chamber was fitted on six healthy, young, asymptomatic participants (five men; 32 ± 6 year), who were normotensive, nonsmoking, in sinus rhythm, free of known cardiovascular or metabolic diseases, and not consuming any acute or chronic medications. A suction of −60 mmHg was applied for 5 s, and the corresponding data were recorded. Before each study visit, the participants were instructed to abstain from caffeine, alcohol, and strenuous exercise for 12–24 h.Results: In all the trials, a significant reflex bradycardia (−10 ± 2 bpm) and depressor response (−15 ± 4 mmHg) to neck suction were observed, consistent with the results in the literature. The neck chamber device operated noiselessly [sound pressure level (SPL) of 34.3 dB] compared to a regular vacuum-cleaner-based system (74.6 dB).Conclusion: Using the proposed approach, consistent blood pressure and heart rate responses to carotid baroreflex hypertensive stimuli could be recorded, as in previous studies conducted using neck collar devices. Furthermore, the neck chamber device operated noiselessly and can thus be applied in hospital environments.
Dual action of Dooku1 on PIEZO1 channel in human red blood cells
Authors: Hatem Aline , Poussereau Gwendal , Gachenot Martin , Pérès Laurent , Bouyer Guillaume , Egée Stéphane 
Published: July 2023

PIEZO1 is a mechanosensitive non-selective cation channel, present in many cell types including Red Blood Cells (RBCs). Together with the Gárdos channel, PIEZO1 forms in RBCs a tandem that participates in the rapid adjustment of the cell volume. The pharmacology allowing functional studies of the roles of PIEZO1 has only recently been developed, with Yoda1 as a widely used PIEZO1 agonist. In 2018, Yoda1 analogues were developed, as a step towards an improved understanding of PIEZO1 roles and functions. Among these, Dooku1 was the most promising antagonist of Yoda1-induced effects, without having any ability to activate PIEZO1 channels. Since then, Dooku1 has been used in various cell types to antagonize Yoda1 effects. In the present study using RBCs, Dooku1 shows an apparent IC50 on Yoda1 effects of 90.7 µM, one order of magnitude above the previously reported data on other cell types. Unexpectedly, it was able, by itself, to produce entry of calcium sufficient to trigger Gárdos channel activation. Moreover, Dooku1 evoked a rise in intracellular sodium concentrations, suggesting that it targets a non-selective cation channel. Dooku1 effects were abolished upon using GsMTx4, a known mechanosensitive channel blocker, indicating that Dooku1 likely targets PIEZO1. Our observations lead to the conclusion that Dooku1 behaves as a PIEZO1 agonist in the RBC membrane, similarly to Yoda1 but with a lower potency. Taken together, these results show that the pharmacology of PIEZO1 in RBCs must be interpreted with care especially due to the unique characteristics of RBC membrane and associated cytoskeleton.
The effects of community-based exercise modalities and volume on musculoskeletal health and functions in elderly people
Authors: Lim Chin Leong , Keong Nicholas Ling Swee , Yap Margaret Mei Chan , Tan Alvin Wai Kit , Tan Cher Heng , Lim Wee Shiong 
Published: July 2023

The effects of different muscle loading exercise (MLEX) modes and volume on musculoskeletal health is not well-studied in older populations.Aim: Therefore, this study aimed to compare the effects of community-based MLEX modalities and volume on musculoskeletal health in elderly people.Methods: Elderly men (n = 86) and women (n = 170), age 50–82 years old, were assigned to the sedentary (SE, n = 60), muscle strengthening exercise (MSE, n = 71), aerobic exercise (AE, n = 62) and Tai Chi exercise (TCE, n = 63) groups, based on &gt; 2 years of exercise history. Exercise volume was compared between “Minimum” (“Min” &lt; 60 min/week), “Low” (60–120 min/week). “Moderate” (121–239 min/week) and “High” (240–720 min/week) volumes.Results: All three modes of MLEX were associated with lower percentage of body fat (BF%) and higher percentage of lean body mass (LBM%, p = 0.003 main effect of group, and p = 0.002 main effect of volume for both BF% and LBM%), but not with higher bone mineral density (BMD, total body, lumbar spine, total hip and neck of femur), than SE. TCE had a distinct advantage in trunk flexibility (p = 0.007 with MSE, p = 0.02 with AE, and p = 0.01 with SE), and both TCE (p = 0.03) and AE (p = 0.03) performed better than SE in the one-leg stand balance test. Isometric strength and throwing speed and peak power with a 2 kg power ball were higher in the MLEX than SE groups (p = 0.01), in the ranking order of MSE, AE and TCE. However, there was no difference in handgrip strength performance between the MLEX groups, which performed better than the SE participants. Accumulating &gt;120 min/week of MLEX can promote body composition health and muscle functions, but 60 min/week of MSE alone may have equal or better outcomes in these parameters.Conclusion: Community-based MLEX classes may be used to mitigate age-related chronic disease that are associated with body composition and muscular functions.
Transcriptome and metabolite analyses indicated the underlying molecular responses of Asian ginseng (Panax ginseng) toward Colletotrichum panacicola infection
Authors: Xia Jinglin , Liu Ning , Han Junyou , Sun Jingyuan , Xu Tianyi , Liu Shouan 
Published: July 2023

Panax ginseng Meyer is one of the most valuable plants and is widely used in China, while ginseng anthracnose is one of the most destructive diseases. Colletotrichum panacicola could infect ginseng leaves and stems and causes serious anthracnose disease, but its mechanism is still unknown. Here, transcriptome and metabolism analyses of the host leaves were conducted to investigate the ginseng defense response affected by C. panacicola. Upon C. panacicola infection, ginseng transcripts altered from 14 to 24 h, and the expression of many defense-related genes switched from induction to repression. Consequently, ginseng metabolites in the flavonoid pathway were changed. Particularly, C. panacicola repressed plant biosynthesis of the epicatechin and naringin while inducing plant biosynthesis of glycitin, vitexin/isovitexin, and luteolin-7-O-glucoside. This work indicates C. panacicola successful infection of P. ginseng by intervening in the transcripts of defense-related genes and manipulating the biosynthesis of secondary metabolites, which might have antifungal activities.
“You are the first person to ask me how I’m doing sexually”: sexual and reproductive health needs and sexual behaviours among migrant people in transit through Panama
Authors: Panchenko Sofya , Mayaud Philippe , Baranyi Nicholls Sebastian , López González Carolina , Ordáz Khatherine Michelle , Baird Madeline , Gabster Amanda 
Published: July 2023

BackgroundUnprecedented numbers of migrant people transiting through the Darién Gap at the Panama-Colombia border were recorded in 2021 and 2022. Data on sexual and reproductive health (SRH) needs and service provision among migrant people in transit is generally extremely sparse. This study aimed to collect personal accounts of sexual behaviours and SRH needs and access to services among migrant people in transit through Panama.MethodsWe conducted a rapid-assessment qualitative study using semi-structured interviews during June-July 2022. Participants were migrant people in transit at three locations across Panama: (i) at the Migrant Reception Station (MRS) in Darién province at the Panama-Colombia border, (ii) in the city of David near the Costa Rica-Panama border, and (iii) at the Costa Rica-Panama border. Migrant peoples (&gt;18 years) were invited to participate using purposive sampling.ResultsOverall, 26 adult migrant people (16 men, 10 women) across the three sites participated in the study. We identified three overarching themes from the interviews: (1) increased need for SRH service provision, (2) experiences of sex, relationships, and transactional sex, and (3) vulnerability to exploitation and sexual violence. All accounts reported that no formal SRH care was present during the journey through the Gap and described as inconsistent at the MRS in Darién. Provision of gynaecological or genital examinations, laboratory testing for urinary tract or STI, and prenatal care were mentioned to be the most pressing needs. Participants reported a change in their sexual behaviour while travelling, whether a decline in sexual libido or preference towards short-term partners. Most female participants recounted constantly fearing sexual violence during the journey through the Gap and several respondents reported witnessing incidents of sexual and other forms of violence.ConclusionThere are significant unmet needs regarding SRH care during the journey of migrant people transiting through the Darién Gap, at the MRS in the Darién province, and across Panama. Provision of antenatal care, rapid testing for HIV/STI, condom distribution, and care for victims of sexual violence would significantly reduce adverse SRH outcomes and improve the well-being of migrant people, even when in transit.
Machine Learning Approaches to Intracranial Pressure Prediction in Patients with Traumatic Brain Injury: A Systematic Review
Authors: Bradley George R. E. , Roldán María , Kyriacou Panayiotis A. 
Published: July 2023

Purpose: Intracranial pressure (ICP) monitoring is a “gold standard” monitoring modality for severe traumatic brain injury (TBI) patients. The capacity to predict ICP crises could further minimise the rate of secondary brain injury and improve the outcomes of TBI patients by facilitating timely intervention prior to a potential crisis. This systematic review sought (i) to identify the most efficacious approaches to the prediction of ICP crises within TBI patients, (ii) to access the clinical suitability of existing predictive models and (iii) to suggest potential areas for future research. Methods: Peer-reviewed primary diagnostic accuracy studies, assessing the performance of ICP crisis prediction methods within TBI patients, were included. The QUADAS-2 tool was used to evaluate the quality of the studies. Results: Three optimal solutions to predicting the ICP crisis were identified: a long short-term memory (LSTM) model, a Gaussian processes (GP) approach and a logistic regression model. These approaches performed with an area under the receiver operating characteristics curve (AUC-ROC) ranging from 0.86 to 0.95. Conclusions: The review highlights the existing disparity of the definition of an ICP crisis and what prediction horizon is the most clinically relevant. Moreover, this review draws attention to the existing lack of focus on the clinical intelligibility of algorithms, the measure of how algorithms improve patient care and how algorithms may raise ethical, legal or social concerns. The review was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42022314278).
General New Results on (ϕ,F)−Contractions in b−Metric-like-Spaces
Authors: Zoto Kastriot , Gardašević-Filipović Milanka , Vardhami Ilir , Mitrović Zoran , Radenović Stojan 
Published: July 2023

Thispaper recognizes a general approach related to recent fixed point results about the classes of interpolative and hybrid contractions in metric space and general metric spaces. Considering auxiliary functions, so called Wardowski functions, and a rich set of implicit relations, we introduce types of (αvq,ϕ,F)−contractions and r−order hybrid (αvq,ϕ,F)−contractions in the setting of b−metric-like spaces. They generate and simplify many forms of contractions widely used in the literature. The resulting theorems significantly extend, generalize, and unify an excellent work on fixed point theory.
Resurrection of Diplostomum numericum Niewiadomska, 1988 (Digenea, Diplostomatoidea: Diplostomidae) Based on Novel Molecular Data from the Type-Host
Authors: Sokolov Sergey G. , Ieshko Evgeny P. , Lebedeva Daria I. 
Published: July 2023

Diplostomum is a taxonomically problematic genus of trematodes, with many members harmful at the metacercarial stage to fish in aquaculture. We found metacercariae in the eye vitreous humor of the rudd, Scardinius erythrophthalmus; the bleak, Alburnus alburnus; and the roach, Rutilus rutilus, in Karelia (Russia) and identified them as Diplostomum numericum based on a combination of morphological and ecological data. Previously, D. numericum was thought to be conspecific with Diplostomum gavium. However, our phylogenetic analysis based on the sequences of the cox1 mitochondrial DNA gene did not support this hypothesis. We demonstrated the conspecificity of D. numericum with the larval trematode Diplostomum sp. Lineage 3 of Blasco-Costa et al. (2014) from the eye vitreous humor of European salmonid and cyprinid fishes. Therefore, we resurrected the species D. numericum and identified Diplostomum sp. Lineage 3 of Blasco-Costa et al. (2014) as D. numericum. Finally, we hypothesized that D. numericum was, in fact, conspecific with Diplostomum colymbi and that the latter was distinct from D. gavium sensu stricto.