bluuebunny/crossref_metadata_2025_split huggingface dataset:
Danlian-Tongmai formula improves diabetic vascular calcification by regulating CCN3/NOTCH signal axis to inhibit inflammatory reaction
Authors: Wang Wenting , Li Yiwen , Zhu Mengmeng , Xu Qian , Cui Jing , Liu Yanfei , Liu Yue 
Published: January 2025

BackgroundVascular calcification (VC) commonly occurs in diabetes and is associated with cardiovascular disease incidence and mortality. Currently, there is no drug treatment for VC. The Danlian-Tongmai formula (DLTM) is a traditional Chinese medicine (TCM) prescription used for diabetic VC (DVC), but its mechanisms of action remain unclear. This study aims to elucidate the effects of DLTM on DVC and explore the underlying mechanisms of action.MethodsUltra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was used to identify the metabolites of DLTM. A DVC rat model was established using streptozotocin (STZ) combined with vitamin D3 (VitD3). The effects of DLTM on DVC were evaluated through alizarin red staining, calcium deposition, and changes in osteogenic and contractile markers. The specific molecular mechanism of DLTM in treating diabetic VC was comprehensively analyzed by transcriptomics, molecular docking and in vivo experimental verification.ResultsWe identified 108 major metabolites of DLTM. In vivo, high-dose DLTM significantly alleviated VC in diabetic rats. Transcriptomic analysis showed that DLTM treatment markedly altered the transcriptomic profile of rat aortas, which was associated with regulating the CCN3/NOTCH signaling pathway, promoting vascular smooth muscle contraction, and inhibiting the inflammatory responses. Molecular docking and molecular dynamics simulation demonstrated strong binding interactions between DLTM metabolites and key molecules within the CCN3/NOTCH pathway, including NOTCH1, DLL1, DLL4, hes1, and hey1. In vivo experiments confirmed that DLTM could upregulate CCN3, inhibit the activation of NOTCH signaling ligands DLL1 and downstream transcription factors hes1 and hey1, and reduce the release of inflammatory cytokines IL6, IL1β, and TNFα.ConclusionDLTM alleviates DVC by regulating the CCN3/NOTCH signaling axis to inhibit inflammatory responses. Our research provides experimental basis for clinical treatment and drug transformation of diabetic VC.
Metabolomics analysis of anaphylactoid reactions induced by Xueshuantong injection in normal and immunocompromised mice
Authors: Guo Xiaoqian , Zhang Chi , Li Yingyu , Wen Wen , He Yinghui , Tang Feng , Chen Chunming , Hu Chao , OuYang Linqi , Liu Wenlong , Zhu Zhenhua , Liu Hongyu 
Published: January 2025

BackgroundXueshuantong injection (Lyophilized) (XSTI) is widely used to treat cardiovascular and cerebrovascular diseases. However, anaphylactoid reactions (ARs) are frequently reported as one of its side effects, and the mechanisms of ARs and their relationship with the different immune status are still not well understood.PurposeThis article aims to examine the sensitizing effect of XSTI, explore the impact of normal and immunocompromised states on ARs, and analyze AR-related metabolic pathways by metabolomics.MethodsAn immunocompromised mouse model was established through intraperitoneal injection of cyclophosphamide (CTX). Normal and immunocompromised mice were then treated with normal saline (NS), histamine (HIS), and XSTI, respectively. Behavioral responses, auricle blue staining, and Evans blue (EB) exudation were used as indices to evaluate the sensitization of XSTI on both normal and immunocompromised mice. Subsequently, ARs models with different immune statuses were established, and validated by measuring four serum indicators using enzyme-linked immunosorbent assay (ELISA). Finally, LC-MS metabolomics analysis was performed on mouse serum to evaluate the metabolic pathways.ResultsThe intensity of ARs induced by XSTI in mice was found to increase with the administered dose, with normal mice exhibiting higher AR intensities compared to immunocompromised mice. Metabolomic analysis revealed significant metabolic changes in XSTI-treated mice. The metabolic pathways predicted from these different metabolites include biotin metabolism, histidine metabolism, glycerolipid metabolism, bile secretion, arachidonic acid metabolism, sphingolipid metabolism, niacin and nicotinamide metabolism, tryptophan metabolism, steroid biosynthesis, and arginine and proline metabolism.ConclusionResearch indicated that the sensitization of XSTI is dose-dependent, and mice with weakened immune functions exhibit lower sensitivity. Through metabolomics research, the differential metabolites in mice were analyzed, and the metabolic pathways inducing ARs were predicted. This study offers guidance on safe medication from the perspective of organism susceptibility and lays a foundation for research on the potential mechanisms of ARs.
Glycyrrhizin as a potential disease-modifying therapy for epilepsy: insights into targeting pyroptosis to exert neuroprotective and anticonvulsant effects
Authors: Wei Lei , Ou Sijie , Meng Youshi , Sun Lanfeng , Zhang Lin , Lu Yuling , Wu Yuan 
Published: January 2025

BackgroundFor patients with epilepsy, antiseizure medication remains the primary treatment; however, it is ineffective in approximately 30% of cases. These patients experience progressive neuronal damage and poor outcomes. Therefore, there is an urgent need for disease-modifying therapy (DMT) that targets the pathogenesis of epilepsy. Glycyrrhizin has shown potential as a DMT in epilepsy due to its multiple targets and diverse mechanisms. Previous studies suggest that glycyrrhizin may regulate key processes involved in epilepsy pathogenesis, such as neuroinflammation and cell death, but its effects on pyroptosis have not been reported.MethodsThis study employed bioinformatics techniques to identify potential molecular targets for glycyrrhizin in epilepsy treatment and then validated using a kainic acid-induced status epilepticus mouse model.ResultsGlycyrrhizin treatment significantly prolonged seizure latency, reduced seizure duration, and alleviated neuronal damage in the status epilepticus mouse model. Molecular experiments indicated that glycyrrhizin may regulate pyroptosis through mediation of the high mobility group box 1 (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling pathway.ConclusionGlycyrrhizin exerts neuroprotective and anticonvulsant effects in epilepsy by regulating pyroptosis via the HMGB1/TLR4/NF-κB signaling pathway, offering novel insights into its potential as a DMT for epilepsy.
The effects of aerobic exercise and heat stress on the unbound fraction of caffeine
Authors: McLaughlin Mackenzie , Dizon Kaye , Jacobs Ira 
Published: January 2025

IntroductionThe fraction of drug circulating in the blood that is not bound to plasma proteins (fu) is considered pharmacologically active since it readily binds to its receptor. In vitro evidence suggests that changes in temperature and pH affect the affinity of drug binding to plasma proteins, resulting in changes in fu. In light of the well-established effects of exercise on body temperature and blood pH, we investigated whether an increase in blood temperature and decrease in pH facilitated through passive heating and exercise translated to a change in the fu of caffeine.MethodsTen healthy participants (4 females and 6 males; age: 21.9 ± 2.7 years [means ± SD]) ingested 3 mg/kg of anhydrous caffeine on two separate occasions comprised of a control trial involving 105 min of rest, and an experimental trial involving 10 min of passive heating, followed by 20 min of cycling at 55% V˙O2peak, and then 10 sprint intervals at 90% V˙O2peak. Venous blood was sampled and the plasma was processed via ultrafiltration to quantify the fu of caffeine and its major metabolite, paraxanthine.ResultsThe exercise protocol resulted in maximal increases in core temperature of 1.37°C ± 0.27°C and lactate of 10.34 ± 3.33 mmol/L, and a decrease in blood pH of 0.12 ± 0.051 (all p &lt; 0.05), which did not affect the fu of caffeine (baseline: 0.86 vs post-exercise: 0.75; p = 0.30) or paraxanthine (baseline: 0.59 vs. post-exercise: 0.70; p = 0.11). Furthermore, the rate of metabolism of caffeine assessed through the metabolic ratio ([paraxanthine]/[caffeine]) did not differ between resting and exercise trials.DiscussionTherefore, the changes in blood temperature and pH in this study did not affect the fu of caffeine or paraxanthine.
Toward a hyperventilation detection system in freediving: a proof of concept using force sensor technology
Authors: Pernett Frank , Mulder Eric , Johansson Filip , Sieber Arne , Bermudez Ricardo , Lossner Marcus , Schagatay Erika 
Published: January 2025

Background and aimHyperventilation before breath-hold diving (freediving) is widely accepted as a risk factor for hypoxic syncope or blackout (BO), but there is no practical way to address it before dives. This study explores the feasibility of using a force sensor to predict end-tidal carbon dioxide (PETCO2) to assess hyperventilation in freedivers.Methods and resultsTwenty-one freedivers volunteered to participate during two national competitions. The divers were instructed to breathe normally and perform three dry apneas of 1, 2, and 3-min duration at 2-min intervals in a sitting position. Before and after the apneas, PETCO2 was recorded. The signal from the force sensor, attached to a chest belt, was used to record the frequency and amplitude of the chest movements, and the product of these values in the 60 s before the apnea was used to predict PETCO2. The mean PETCO2 was below 35 mmHg before all apneas. The mean amplitude of the signal from the force sensor increased from apnea 1 to apnea 3 (p &lt; 0.001), while the respiratory rate was similar (NS). The product of the respiratory rate and amplitude from the force sensor explained 34% of the variability of the PETCO2 in the third apnea.ConclusionThis study shows that a force sensor can estimate hyperventilation before static apnea, providing a basis for further research. More studies are needed to confirm its effectiveness in preventing issues. Freedivers may hyperventilate without noticing it, and such a system could improve awareness of this condition. Additional underwater tests are essential to determine whether this system can enhance safety in freediving.
Lesion classification and diabetic retinopathy grading by integrating softmax and pooling operators into vision transformer
Authors: Liu Chong , Wang Weiguang , Lian Jian , Jiao Wanzhen 
Published: January 2025

IntroductionDiabetic retinopathy grading plays a vital role in the diagnosis and treatment of patients. In practice, this task mainly relies on manual inspection using human visual system. However, the human visual system-based screening process is labor-intensive, time-consuming, and error-prone. Therefore, plenty of automated screening technique have been developed to address this task.MethodsAmong these techniques, the deep learning models have demonstrated promising outcomes in various types of machine vision tasks. However, most of the medical image analysis-oriented deep learning approaches are built upon the convolutional operations, which might neglect the global dependencies between long-range pixels in the medical images. Therefore, the vision transformer models, which can unveil the associations between global pixels, have been gradually employed in medical image analysis. However, the quadratic computation complexity of attention mechanism has hindered the deployment of vision transformer in clinical practices. Bearing the analysis above in mind, this study introduces an integrated self-attention mechanism with both softmax and linear modules to guarantee efficiency and expressiveness, simultaneously. To be specific, a portion of query and key tokens, which are much less than the original query and key tokens, are adopted in the attention module by adding a set of proxy tokens. Note that the proxy tokens can fully utilize both the advantages of softmax and linear attention.ResultsTo evaluate the performance of the presented approach, the comparison experiments between state-of-the-art algorithms and the proposed approach are conducted. Experimental results demonstrate that the proposed approach achieves superior outcome over the state-of-the-art algorithms on the publicly available datasets.DiscussionAccordingly, the proposed approach can be taken as a potentially valuable instrument in clinical practices.
Psychological well-being and academic performance of Ukrainian medical students under the burden of war: a cross-sectional study
Authors: Korda Mykhaylo , Shulhai Arkadii , Shevchuk Oksana , Shulhai Oleksandra , Shulhai Anna-Mariia 
Published: January 2025

IntroductionThe mental health of medical students is a key factor for academic performance and the delivery of high-quality medical care in the future. Globally, medical students face numerous challenges that can affect their education. Living and studying facing the war has a crucial influence on medical students’ education and daily life. The study aimed to determine the psychological well-being and academic achievements of Ukrainian medical students who lived in the rear areas after the 18 months of the Russian–Ukrainian war.MethodsThe cross-sectional study was conducted at I.Ya. Horbachevsky Ternopil National Medical University. We analyzed the psychological well-being and educational achievements of medical students from the second to fifth year of Medical Faculty using the self-report scales DASS-21 and IES-R. A total of 776 students filled out the DASS-21 scale and 491 IES-R scale, respectively.ResultsFollowing the first 18 months of the war, 62.5, 59.6, and 58.8% of Ukrainian medical students self-reported signs of stress, anxiety, and depression, respectively. Severe and extremely severe depressive symptoms were observed in 25.6% of students, anxiety in 31.9%, and stress in 29.7%, with a higher prevalence among female students. Additionally, 44.2% of responders had significant symptoms of post-traumatic stress disorder, with the highest scores on the hyperarousal subscale (&gt;37). Academic performance in 2023 was significantly lower compared to the pre-war period in 2019 (p &lt; 0.001) (p = 0.000). The multiple linear regression analysis showed that academic performance was positively associated with depression (p = 0.003), hyperarousal (p &lt; 0.001), anxiety (p = 0.03), and negatively associated with stress (p = 0.002).ConclusionUkrainian medical students in rear areas are facing various challenges, with war-related stressors having a profound impact on their mental health. Our findings have shown an increasing prevalence of anxiety, stress, depression, and symptoms of post-traumatic stress disorder, all of which may negatively affect academic performance. The educational process during wartime is important for facilitating qualified medical personnel and quality healthcare. Understanding the burden of war allows for the development of wellness programs that support student mental health in conflict zones.
Determining the risk factors of malaria and anemia in children between 6 and 59 months using the joint generalized linear mixed model on the 2021 Nigeria Malaria Indicator Survey dataset
Authors: Mhelembe Talani , Ramroop Shaun , Habyarimana Faustin 
Published: January 2025

BackgroundMalaria and anemia are significant public health concerns that contribute to child mortality in African. Despite global efforts to control the two diseases, their prevalence in high-risk regions like Nigeria remains high. Understanding socioeconomic, demographic, and geographical factors associated with malaria and anemia, is critical for effective intervention strategies.ObjectiveThe study aims to assess the risk factors for malaria and anemia in children under 5 years using the joint generalized linear mixed model (JGLMM).MethodsThe Nigeria Malaria Indicator Survey (NMIS) 2021 dataset was used, with a sample of 10,120 children aged 6–59 months. A two-stage sampling method was applied. Descriptive statistics and chi-square tests examined factors associated with malaria and anemia prevalence. Missing data were handled using multiple imputations with chained equations (MICE). Lastly, the adjusted odds ratio was interpreted for the current study. SAS was used in analyzing the data and statistical significance was set at 5% significance level.ResultsThe prevalence of malaria and anemia was 36.81 and 67.66%, respectively, in children between 6 and 59 months old in Nigeria. The JGLMM was used to examine malaria RDT and anemia findings in conjunction with demographic, geographic, and socioeconomic covariates. The following underlying risk factors for malaria and anemia in children were discovered in the study: region, altitude, age of child in months, toilet facility of the household, main wall material used for the house, main roof material used for the house, children under five who slept under a mosquito net, whether the child had fever in last 2 weeks before the survey took place, place of residence where the child resides, household wealth index, sex of child, and mother’s education level. However, whether the mother knew of ways to prevent malaria was not statistically significant regarding anemia.ConclusionThis study highlights the importance of addressing fever as a key factor for anemia and improving housing conditions to reduce malaria and anemia prevalence. Policymakers should prioritize mosquito net distribution and healthcare access, particularly in rural areas. The study’s novelty lies in its handling of missing data through imputation techniques, enhancing the reliability of findings.
Research on the impact of urban innovation on public health
Authors: Zhao Liang , Li Chen , Qian Yaosen 
Published: January 2025

IntroductionThis article explores the impact of innovation on urban public health, with a particular focus on panel data from 15 sub-provincial cities in China. The study aims to provide scientific evidence for policymakers by analyzing how technological innovation affects urban public health levels.MethodsThe study used a panel model for empirical analysis which based on panel data from 15 sub provincial cities across the country, using the number of doctors per 10,000 people and per capita financial medical and health expenditure as proxy variables for urban public health, and using the level of technological development as the core explanatory variable for regression analysis.ResultsThe research results show that: (1) for public health quantified by the number of doctors per 10,000 people in cities, innovation does not have a significant promoting effect on urban public health; (2) Compared to the number of doctors per 10,000 people in a region, the per capita financial expenditure on healthcare can better measure the level of urban public health; (3) Innovation has a significant impact on urban public health, measured by per capita fiscal expenditure on healthcare.DiscussionIn order to transform technological innovation into a driving force for the development of urban public health, efforts must be made from multiple aspects. Currently, building a strong foundation for people’s health relies on the support of science and technology, and enhancing innovation as a primary driving force is crucial. China urgently needs to improve the stability and competitiveness of its pharmaceutical industry and supply chain, break through key core technologies, and take the initiative in the future development of the pharmaceutical industry.
Gameplay and physical activity behaviors in adult video game players
Authors: Scoggins Haylei , Porter Ryan R. , Braun-Trocchio Robyn 
Published: January 2025

IntroductionSince the early 2000s, the video game industry has seen extraordinary booms in product development and market growth, with the total number of video game players globally reaching 2.69 billion by the end of 2020. Despite the rapid growth of the industry, there is little recent data investigating the time adult video game players spend sedentary playing video games and the time they spent engaged in physical activity. The purpose of this quantitative, cross-sectional, non-experimental survey study is to describe the frequency and duration of video game play and physical activity in adult video game players.MethodsParticipants completed an online survey, evaluating their demographic and health history information, video game play, and physical activity behaviors.ResultsThe study used data from a total of 221 participants (Males = 153, Females = 68). The mean age of the participants was 27.29 (SD 7.27) years. Of the 221 participants, 145 identified as casual players, 50 amateurs, 24 semi-professionals, and 2 professionals. The participants spent over five days per week and an average of 26.56 h per week playing video games. Personal computers were reported to have the longest duration of play of the four platforms investigated (17.59 h per week). The total amount of time participants spent engaged in cumulative moderate-to-vigorous physical activity (MVPA) was an average of 15.43 (SD 16.79) hours per week. The majority of this time was spent engaged in occupational physical activity (5.11 h per week). Participants spent 2.39 h per week engaged in leisure time MVPA.ConclusionOur results indicate an increase in VG play compared to 2018, suggesting United States adult video game players may be more at risk for detrimental effects to their physical health. This could be attributed to the habits formed during the COVID-19 pandemic, the influences from video genre game play mechanics, and the social aspects of playing video games with friends. Future research should focus on developing research methodologies that will objectively measure adult video game player frequencies and durations in video game play alongside extensive observation of different video gameplay mechanic genres and their relationships with physical activity.
Case Report: Robot-assisted laparoscopic bladder diverticulectomy: a case series and initial experience
Authors: Ge Guangju , Wang Haihong , Zheng Qiming , Zhang Shuai , Wang Huan , Ma Liang 
Published: January 2025

ObjectivesTo explore the experience of tumor control technique in robot-assisted laparoscopic bladder diverticulectomy (RALBD) in the treatment of bladder diverticulum tumor, intraoperative tumor control and postoperative comprehensive treatment.Patients and methodsWe treated three male patients with bladder diverticulum tumors. Case 1 involved a 63-year-old with a 3.0 cm tumor in the diverticulum on the right bladder wall. Case 2 involved a 70-year-old with a 1.0 cm cauliflower-like tumor in the diverticulum on the left bladder wall. Case 3 involved a 64-year-old with a 3.0 cm tumor in the diverticulum on the right bladder wall. Each patient underwent robot-assisted laparoscopic partial cystectomy (PC) with ureteral Double J (D-J) stent placement. To minimize the risk of intraoperative tumor spread, we implemented enhanced surgical techniques. Systemic chemotherapy and adjuvant intravesical chemotherapy were recommended to reduce the risk of tumor recurrence and metastasis.ResultsPostoperative pathology confirmed papillary urothelial carcinoma in all three cases. Each patient was followed up for over 20 months, with no evidence of recurrence or distant metastasis observed through cystoscopy and chest and abdominal CT scans.ConclusionFor patients with urothelial carcinoma in a bladder diverticulum, robot-assisted laparoscopic bladder-sparing surgery is a viable option when appropriate cases are selected. Effective intraoperative tumor control and comprehensive postoperative treatment are crucial to minimizing recurrence and metastasis risks. The robotic approach offers enhanced precision and visualization compared to traditional open or laparoscopic techniques, potentially leading to improved outcomes regarding intraoperative tumor control and reduced postoperative complications. However, this study is limited by its small sample size of only three patients and short-term follow-up. A larger sample of patients is needed to confirm the advantages of the robotic approach.