bluuebunny/crossref_metadata_2025_split huggingface dataset:
CX3CL1 release during immunogenic apoptosis is associated with enhanced anti-tumour immunity
Authors: Naessens Faye , Demuynck Robin , Vershinina Olga , Efimova Iuliia , Saviuk Mariia , De Smet Greet , Mishchenko Tatiana A. , Vedunova Maria V. , Krysko Olga , Catanzaro Elena , Krysko Dmitri V. 
Published: July 2024

IntroductionImmunogenic cell death (ICD) has emerged as a novel option for cancer immunotherapy. The key determinants of ICD encompass antigenicity (the presence of antigens) and adjuvanticity, which involves the release of damage-associated molecular patterns (DAMPs) and various cytokines and chemokines. CX3CL1, also known as neurotactin or fractalkine, is a chemokine involved in cellular signalling and immune cell interactions. CX3CL1 has been denoted as a “find me” signal that stimulates chemotaxis of immune cells towards dying cells, facilitating efferocytosis and antigen presentation. However, in the context of ICD, it is uncertain whether CX3CL1 is an important mediator of the effects of ICD.MethodsIn this study, we investigated the intricate role of CX3CL1 in immunogenic apoptosis induced by mitoxantrone (MTX) in cancer cells. The Luminex xMAP technology was used to quantify murine cytokines, chemokines and growth factors to identify pivotal regulatory cytokines released by murine fibrosarcoma MCA205 and melanoma B16-F10 cells undergoing ICD. Moreover, a murine tumour prophylactic vaccination model was employed to analyse the effect of CX3CL1 on the activation of an adaptive immune response against MCA205 cells undergoing ICD. Furthermore, thorough analysis of the TCGA-SKCM public dataset from 98 melanoma patients revealed the role of CX3CL1 and its receptor CX3CR1 in melanoma patients.ResultsOur findings demonstrate enhanced CX3CL1 release from apoptotic MCA205 and B16-F10 cells (regardless of the cell type) but not if they are undergoing ferroptosis or accidental necrosis. Moreover, the addition of recombinant CX3CL1 to non-immunogenic doses of MTX-treated, apoptotically dying cancer cells in the murine prophylactic tumour vaccination model induced a robust immunogenic response, effectively increasing the survival of the mice. Furthermore, analysis of melanoma patient data revealed enhanced survival rates in individuals exhibiting elevated levels of CD8+ T cells expressing CX3CR1.ConclusionThese data collectively underscore the importance of the release of CX3CL1 in eliciting an immunogenic response against dying cancer cells and suggest that CX3CL1 may serve as a key switch in conferring immunogenicity to apoptosis.
Association of inflammatory score with all-cause and cardiovascular mortality in patients with metabolic syndrome: NHANES longitudinal cohort study
Authors: Chen Yan , Ju Haonan , Xie Kailing , Zhao Xin 
Published: July 2024

BackgroundInflammatory scores are known to reflect the systemic inflammatory burden. Despite this, the association between the inflammatory score and the risk of all-cause and cardiovascular mortality in patients with metabolic syndrome (MetS) remains poorly understood. To address this gap in the literature, this study investigated this potential association between these two factors.MethodsA total of 3401 patients with MetS from the National Health and Nutrition Examination Survey (1999–2010) were enrolled. Survival status and cause of death were obtained by linking data from the National Death Index (NDI). The inflammatory score was calculated based on the sum of the Z-scores for white blood cell (WBC) count and C-reactive protein (CRP) at baseline. The patients were divided into inflammatory score quartiles. Cox proportional hazards regression was used to determine the association between inflammatory score and mortality. Restricted cubic splines (RCS) were used to explore the dose-response relationship between inflammatory score and mortality. Stratified analyses and interaction tests were conducted according to sex, age, body mass index (BMI), alcohol consumption, smoking status, hypertension, diabetes, and stroke status.ResultsAfter a mean follow-up of 145.9 months, 1039 all-cause deaths and 295 cardiovascular deaths were recorded. The results of multivariate Cox regression analysis showed that compared to the lowest quartile (Q1), patients in the highest quartile (Q4) had a 1.74-fold increased risk of all-cause mortality (Model 3: HR = 1.74, 95%CI 1.30–2.32, P &lt; 0.001) and a 1.87-fold increased risk of cardiovascular mortality (Model 3: HR = 1.87, 95%CI 1.12–3.13, P = 0.020). There was a ‘J’-shaped nonlinear relationship between the inflammatory score and all-cause mortality (P for nonlinearity = 0.001), and a marginally significant ‘J’-shaped relationship with cardiovascular mortality (P for nonlinearity = 0.057). The threshold points of the inflammatory score for adverse outcomes were - 0.643 and - 0.621, respectively.ConclusionThe inflammatory score is independently associated with increased all-cause and cardiovascular mortality in patients with MetS, and risk stratification of these patients using inflammatory scores may provide specific therapeutic strategies to improve their prognosis.
Optimization of liquid cooled heat dissipation structure for vehicle energy storage batteries based on NSGA-II
Authors: Sun Guanhua , Peng Jinzhao 
Published: July 2024

Introduction: With the development of the new energy vehicle industry, the research aims to improve the energy utilization efficiency of electric vehicles by optimizing their composite power supply parameters.Methods: An optimization model based on non-dominated sorting genetic algorithm II was designed to optimize the parameters of liquid cooling structure of vehicle energy storage battery. The objective function and constraint conditions in the optimization process were defined to maximize the heat dissipation performance of the battery by establishing the heat transfer and hydrodynamic model of the electrolyzer.Results: The results showed that the optimization method had excellent performance on multiple evaluation indicators, the material degradation rate after optimization was reduced by 42%, the corrosion rate was reduced by 36%, and the battery life was increased by 17%. The optimization method ensured the maximum temperature control for the safe operation of the lithium-ion battery pack. The temperature of the battery pack was effectively controlled. The temperature difference was kept within 5°C, preventing the battery from overheating and extending its service life.Discussion: The proposed liquid cooling structure design can effectively manage and disperse the heat generated by the battery. This method provides a new idea for the optimization of the energy efficiency of the hybrid power system. This paper provides a new way for the efficient thermal management of the automotive power battery.
Discussion of the classification of pediatric drug clinical trials in children's hospitals in China
Authors: Yang Yong , Jiang Rui , Bai Gengliang , Liu Qingqing , Chen Yongfa 
Published: July 2024

ObjectivesThis study aimed to gain insights into pediatric clinical trials conducted in children's hospitals in China and provide valuable references for the development of children's hospitals and the research and development of pediatric drugs.MethodsA comprehensive search was performed on the Chinese Clinical Trial Registry (Chi CTR) and ChinaDrugTrials.org.cn to collect information on all clinical trials involving subjects under 18 years, including those conducted in children's hospitals. The retrieval period was extended until 31 December 2022.ResultsA total of 459 pediatric clinical trials were collected, comprising 299 from Chi CTR and 160 from the Drug Clinical Trial Registration and Information Publicity Platform (Information Platform). Post-marketing drug studies and phase III clinical trials accounted for the majority of research stages. These trials covered a wide range of diseases/systems, with a particular focus on respiratory system disorders, tumors, endocrine disorders, and nutritional or metabolic diseases. Chemical drugs constituted the most extensively studied category, while traditional Chinese medicine/natural drugs received comparatively less attention. Clinical trial activities were primarily geographically focused on the eastern coastal regions of China, with multicenter trials being the most predominant. Ethics committee approval was obtained for 427 studies.ConclusionThe pediatric clinical trials conducted by children's hospitals in China have shown an overall upward trend; however, there is limited research focusing on traditional Chinese medicine, along with significant regional and institutional imbalances. Furthermore, there is still room for improvement regarding ethical review processes. It is recommended that children's hospitals enhance their scientific research capabilities while optimizing resource allocation to meet medical service demands effectively. Additionally, fostering more research-focused children's hospitals will contribute to the high-quality development of children's health in China.
Excessive daytime sleepiness in myotonic dystrophy: a narrative review
Authors: Hoxhaj Domeniko , Pascazio Alessia , Maestri Michelangelo , Ricci Giulia , Fabbrini Monica , Torresi Francesca Buracchi , Siciliano Gabriele , Bonanni Enrica 
Published: July 2024

IntroductionExcessive daytime sleepiness (EDS) is a common and debilitating symptom in both forms of myotonic dystrophy (DM), significantly impacting patients’ quality of life. The review focuses on the purpose of examining the current understanding of EDS in these conditions, the difficulty in correctly accessing it, the recent findings related to its etiology and prevalence, and a summary of potential therapeutic implications.MethodsWe conducted a comprehensive search through PubMed, selecting studies that provided significant insights into the mechanisms, prevalence, and management of EDS in DM1 and DM2.Results and discussionEDS is highly prevalent in both DM1 and DM2. Polysomnographic studies have revealed prominent dysregulation of REM sleep in DM1, suggesting a possible narcoleptic-like phenotype and alterations in NREM sleep that contributes to daytime sleepiness. Other factors have been proposed to explain EDS in DM1, including dysregulation of the sleep-wake circadian rhythm through nocturnal actigraphy analysis. The central origin of EDS is increasingly delineated supported by serotonin and orexin pathways dysfunction, and recent neuroradiological findings showing that in DM1 hippocampus volume was positively correlated with self-reported fatigue and somnolence. Sleep-disordered breathing and respiratory dysfunctions are prevalent in DM, their direct correlation with EDS remains complex and inconclusive, but respiratory evaluation should be recommended if obstructive sleep apneas or respiratory muscle dysfunctions are suspected. Drug interventions, such as modafinil and mexiletine, have shown promise in managing excessive daytime sleepiness and reducing myotonia without significant cardiac conduction effects. Enhancing EDS management in myotonic dystrophy is key to improving overall patient well-being.
Simulating tDCS electrode placement to stimulate both M1 and SMA enhances motor performance and modulates cortical excitability depending on current flow direction
Authors: Sato Takatsugu , Katagiri Natsuki , Suganuma Saki , Laakso Ilkka , Tanabe Shigeo , Osu Rieko , Tanaka Satoshi , Yamaguchi Tomofumi 
Published: July 2024

IntroductionThe conventional method of placing transcranial direct current stimulation (tDCS) electrodes is just above the target brain area. However, this strategy for electrode placement often fails to improve motor function and modulate cortical excitability. We investigated the effects of optimized electrode placement to induce maximum electrical fields in the leg regions of both M1 and SMA, estimated by electric field simulations in the T1and T2-weighted MRI-based anatomical models, on motor performance and cortical excitability in healthy individuals.MethodsA total of 36 healthy volunteers participated in this randomized, triple-blind, sham-controlled experiment. They were stratified by sex and were randomly assigned to one of three groups according to the stimulation paradigm, including tDCS with (1) anodal and cathodal electrodes positioned over FCz and POz, respectively, (A-P tDCS), (2) anodal and cathodal electrodes positioned over POz and FCz, respectively, (P-A tDCS), and (3) sham tDCS. The sit-to-stand training following tDCS (2 mA, 10 min) was conducted every 3 or 4 days over 3 weeks (5 sessions total).ResultsCompared to sham tDCS, A-P tDCS led to significant increases in the number of sit-to-stands after 3 weeks training, whereas P-A tDCS significantly increased knee flexor peak torques after 3 weeks training, and decreased short-interval intracortical inhibition (SICI) immediately after the first session of training and maintained it post-training.DiscussionThese results suggest that optimized electrode placement of the maximal EF estimated by electric field simulation enhances motor performance and modulates cortical excitability depending on the direction of current flow.
Unfavorable food consumption in children up to school entry age: results from the nationwide German KiESEL study
Authors: Spiegler Clarissa , Jansen Sara , Burgard Leonie , Wittig Friederike , Brettschneider Anna-Kristin , Schlune Andrea , Heuer Thorsten , Straßburg Andrea , Roser Silvia , Storcksdieck Genannt Bonsmann Stefan , Ensenauer Regina 
Published: July 2024

IntroductionEvidence points toward the early life being crucial for preventing nutrition-related diseases. As promotion of healthier food preferences in toddlerhood and preschool age might still modulate the trajectories of disease risk, understanding diet in these age groups is necessary. The objective was to analyze food consumption and diet quality of 1–5-year-old children living in Germany in relation to age and sex.MethodsData from 890 children, a subsample of the representative, cross-sectional Children’s Nutrition Survey to Record Food Consumption (KiESEL) conducted by the German Federal Institute for Risk Assessment in 2014–2017, were analyzed. Dietary data were collected using food records (3 consecutive plus 1 independent day). Diet quality was evaluated against the German food-based dietary guidelines (FBDG).ResultsConsumption of unfavorable foods (e.g., sweets, soft drinks) exceeded the recommended maximum of 10% of energy intake (E%) by a multiple in all age and sex groups (medians: 24.8–35.8 E%). Preschoolers consumed more unfavorable foods than toddlers and boys more than girls. More than half of the children exceeded the recommendation for meat intake (medians: 2.3–3.2% of the total food consumption (%TFC) vs. 2 %TFC), especially preschoolers. In nearly all children, vegetable consumption was too low (medians: 4.2–4.5 %TFC vs. 12 %TFC). Also, milk/milk product consumption was below recommendations, more so in preschoolers (median: 12.0 %TFC ♂, 11.9 %TFC ♀ vs. 18 %TFC) than in toddlers (median: 16.1 %TFC ♂, 19.6 %TFC ♀). In toddlers and preschoolers with overweight or obesity, adherence to dietary recommendations of these food groups was largely similar to that of the total sample. Overall, 5-year-olds showed an unhealthier dietary pattern than 1-year-olds, which already emerged at age 2 years and became more evident at age 3 years.DiscussionAn adverse dietary pattern arises and even deteriorates at a very young age, showing sex-specific aspects. High attention from public health and research needs to be given to toddlerhood and even earlier life phases, e.g., to develop more age-specific FBDGs, aiming at reducing unhealthy food consumption.
Correlation between fasting blood glucose level and risk of breast cancer in women: a single-center, prospective cohort study
Authors: Li Gefei , Yin Mingjie , Fan Zhimin , Qu Fengjiang 
Published: July 2024

PurposeWe prospectively analyzed the correlation between fasting plasma glucose (FPG) and the risk of breast cancer in women; explored the independent risk factors for breast cancer in women, and compared the effect of FPG level on the risk of young and non-young breast cancer. Our study provides new evidence and ideas for research into breast cancer etiology in China, improves the accuracy of secondary prevention of breast cancer, and provides options for the clinical diagnosis and treatment of breast cancer patients with diabetes.Materials and methodsThree cohorts of women participating in the first health examination of the Kailuan Group in 2006, 2008 and 2010 were assembled to conduct a descriptive analysis of the baseline data on FPG. The cumulative incidence of breast cancer in different groups over 13 years was calculated using the Kaplan-Meier method and groups were compared using the log-rank test. A Cox proportional hazards regression model was used to analyze the association between FPG level and the risk of breast cancer.ResultsThe cumulative incidence of breast cancer increased in people with FPG higher than 5.29 mmol/L, but there was no significant difference in the effect of different levels of FPG on the risk of young breast cancer in the population. Different degrees of fasting glucose can affect the risk of non-young breast cancer in the population.ConclusionThe results of this study suggest that the risk of breast cancer can be reversed by early intervention to control levels of FPG. Regular monitoring of FPG may reduce the misdiagnosis rate of breast cancer in the population.
Non-small cell lung cancer cells and concomitant cancer therapy induce a resistance-promoting phenotype of tumor-associated mesenchymal stem cells
Authors: Sentek Hanna , Braun Annika , Budeus Bettina , Klein Diana 
Published: July 2024

IntroductionThe tumor microenvironment gained attraction over the last decades as stromal cells significantly impact on tumor development, progression and metastasis, and immune evasion as well as on cancer therapy resistance. We previously reported that lung-resident mesenchymal stem cells (MSCs) were mobilized and activated in non-small cell lung cancer (NSCLC) progression and could even mediate radiation resistance in co-cultured NSCLC cells.MethodsWe investigated how MSCs were affected by NSCLC cells in combination with cancer (radiation) therapy in indirect co-cultures using tumor-conditioned medium and Transwells or direct three-dimensional NSCLC–MSC spheroid co-cultures in order to unravel the resistance-mediating action of tumor-associated MSCs.ResultsAlthough no obvious phenotypic and functional alterations in MSCs following NSCLC co-culture could be observed, MSC senescence was induced following co-applied radiotherapy (RT). Global gene expression profiling, in combination with gene set enrichment analysis upon treatment, was used to confirm the senescent phenotype of irradiated MSC and to reveal relevant senescence-associated secretory phenotype (SASP) factors that could meditate NSCLC RT resistance. We identified senescent tumor-associated MSC-derived serine proteinase inhibitor (serpin) E1/PAI1 as potential SASP factor mediating NSCLC progression and RT resistance.DiscussionSpecified intra-tumor–stroma interactions and cell type-specific pro-tumorigenic functions could not only improve lung cancer classification but could even be used for a more precise profiling of individual patients, finally paving an additional way for the discovery of potential drug targets for NSCLC patients.
A high reticulocyte count is a risk factor for the onset of metabolic dysfunction-associated steatotic liver disease: Cross-sectional and prospective studies of data of 310,091 individuals from the UK Biobank
Authors: Ma Peng-Cheng , Li Qi-Mei , Li Rui-Ning , Hong Chang , Cui Hao , Zhang Zi-Yong , Li Yan , Xiao Lu-Shan , Zhu Hong , Zeng Lin , Xu Jun , Lai Wei-Nan , Liu Li 
Published: July 2024

Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) poses a considerable health risk. Nevertheless, its risk factors are not thoroughly comprehended, and the association between the reticulocyte count and MASLD remains uncertain. This study aimed to explore the relationship between reticulocyte count and MASLD.Methods: A total of 310,091 individuals from the UK Biobank were included in this cross-sectional study, and 7,316 individuals were included in this prospective study. The cross-sectional analysis categorized reticulocyte count into quartiles, considering the sample distribution. Logistic regression models examined the connection between reticulocyte count and MASLD. In the prospective analysis, Cox analysis was utilized to investigate the association.Results: Our study findings indicate a significant association between higher reticulocyte count and an elevated risk of MASLD in both the cross-sectional and prospective analyses. In the cross-sectional analysis, the adjusted odds ratios (ORs) of MASLD increased stepwise over reticulocyte count quartiles (quartile 2: OR 1.22, 95% CI 1.17–1.28, p &lt; 0.001; quartile 3: OR 1.44; 95% CI 1.38–1.51, p &lt; 0.001; quartile 4: OR 1.66, 95% CI 1.59–1.74, p &lt; 0.001). The results of prospective analyses were similar.Conclusion: Increased reticulocyte count was independently associated with a higher risk of MASLD. This discovery offers new insights into the potential of reticulocytes as biomarkers for MASLD.
In Vitro evaluation of the anti-pancreatic cancer activity of epimedium herb
Authors: Chen Yangfeng , Xia Han , Zhong Xiaohong 
Published: July 2024

Introduction: Pancreatic cancer (PC) is a particularly aggressive malignancy with limited therapeutic options. The search for innovative treatments has focused on traditional Chinese medicine, specifically epimedium. This research investigates epimedium’s active ingredients, potential targets, and underlying mechanisms in treating PC.Methods: High-performance liquid chromatography (HPLC) was used to quantify the active components of epimedium and HPLC-Q-TOF-MS was employed for qualitative identification. Potential targets of epimedium’s active ingredients were identified using the TCMSP, ETCM, CTD, and Swiss Target Prediction databases. Potential PC-related targets were sourced from DisGeNET, GeneCards, and OMIM databases. A Venn diagram was utilized to identify overlapping PC-related and epimedium targets. Core targets and pathways were elucidated through protein-protein interaction (PPI) network analysis, Gene Ontology (GO) assessments, and Reactome pathway enrichment analyses. Molecular docking techniques investigated interactions between active compounds and these targets. The expression and prognostic implications of target genes were evaluated using GEPIA2 and the Human Protein Atlas (HPA) databases. In vitro studies assessed the impact of epimedium extract (EPE) on Panc-1 cell viability, and Western blot analysis examined the expression levels of key targets.Results: Network pharmacological indicate that epimedium econtains active components such as baohuoside I, icariin, hyperoside, and epimedin B, which have potential therapeutic effects against PC. In vitro assays confirmed that EPE significantly reduced the viability of Panc-1 cells. Western blot analysis revealed a considerable decrease in the expression of key targets in EPE-treated cells, including AKT1, EGFR, p-EGFR, JUN, BCL2, IL6, and SRC. The R-HSA-1280215: Interleukin-4 and Interleukin-13 signaling pathways involving these genes were identified as potential therapeutic targets.Discussion:Epimedium holds promise as a candidate for treating PC. The modulation of interleukin-4 and interleukin-13 signaling pathways could be a pivotal mechanism by which epimedium impedes tumor development. Further research is warranted to validate these findings and explore the clinical applicability of epimedium in PC treatment.