bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancing ASPP2 promotes acute liver injury via an inflammatory immunoregulatory mechanism
Authors: Zhang Xiangying , Xu Ling , Fan Zihao , Gao Yao , Tian Yuan , Cao Yaling , Chen Dexi , Ren Feng 
Published: May 2024

BackgroundAcute liver injury (ALI), which is a type of inflammation-mediated hepatocellular injury, is a clinical syndrome that results from hepatocellular apoptosis and hemorrhagic necrosis. Apoptosis stimulating protein of p53-2 (ASPP2) is a proapoptotic member of the p53 binding protein family. However, the role of ASPP2 in the pathogenesis of ALI and its regulatory mechanisms remain unclear.MethodsThe expression of ASPP2 were compared between liver biopsies derived from patients with CHB, patients with ALI, and normal controls. Acute liver injury was modelled in mice by administration of D-GalN/LPS. Liver injury was demonstrated by serum transaminases and histological assessment of liver sections. ASPP2-knockdown mice (ASPP2+/−) were used to determine its role in acute liver injury. Mouse bone marrow macrophages (BMMs) were isolated from wildtype and ASPP2+/- mice and stimulated with LPS, and the supernatant was collected to incubate with the primary hepatocytes. Quantitative real-time PCR and western blot were used to analyze the expression level of target.ResultsThe expression of ASPP2 was significantly upregulated in the liver tissue of ALI patients and acute liver injury mice. ASPP2+/- mice significantly relieved liver injury through reducing liver inflammation and decreasing hepatocyte apoptosis. Moreover, the conditioned medium (CM) of ASPP2+/- bone marrow-derived macrophages (BMMs) protected hepatocytes against apoptosis. Mechanistically, we revealed that ASPP2 deficiency in BMMs specifically upregulated IL-6 through autophagy activation, which decreased the level of TNF-α to reduce hepatocytes apoptosis. Furthermore, up-regulation of ASPP2 sensitizes hepatocytes to TNF-α-induced apoptosis.ConclusionOur novel findings show the critical role of ASPP2 in inflammatory immunoregulatory mechanism of ALI and provide a rationale to target ASPP2 as a refined therapeutic strategy to ameliorate acute liver injury.
Synthetic BSA-conjugated disaccharide related to the Streptococcus pneumoniae serotype 3 capsular polysaccharide increases IL-17A Levels, γδ T cells, and B1 cells in mice
Authors: Akhmatova Nelli K. , Kurbatova Ekaterina A. , Zaytsev Anton E. , Akhmatova Elina A. , Yastrebova Natalya E. , Sukhova Elena V. , Yashunsky Dmitriy V. , Tsvetkov Yury E. , Nifantiev Nikolay E. 
Published: May 2024

The disaccharide (β-D-glucopyranosyluronic acid)-(1→4)-β-D-glucopyranoside represents a repeating unit of the capsular polysaccharide of Streptococcus pneumoniae serotype 3. A conjugate of the disaccharide with BSA (di-BSA conjugate) adjuvanted with aluminum hydroxide induced — in contrast to the non-adjuvanted conjugate — IgG1 antibody production and protected mice against S. pneumoniae serotype 3 infection after intraperitoneal prime-boost immunization. Adjuvanted and non-adjuvanted conjugates induced production of Th1 (IFNγ, TNFα); Th2 (IL-5, IL-13); Th17 (IL-17A), Th1/Th17 (IL-22), and Th2/Th17 cytokines (IL-21) after immunization. The concentration of cytokines in mice sera was higher in response to the adjuvanted conjugate, with the highest level of IL-17A production after the prime and boost immunizations. In contrast, the non-adjuvanted conjugate elicited only weak production of IL-17A, which gradually decreased after the second immunization. After boost immunization of mice with the adjuvanted di-BSA conjugate, there was a significant increase in the number of CD45+/CD19+ B cells, TCR+ γδ T cell, CD5+ В1 cells, and activated cells with MHC II+ expression in the spleens of the mice. IL-17A, TCR+ γδ T cells, and CD5+ В1 cells play a crucial role in preventing pneumococcal infection, but can also contribute to autoimmune diseases. Immunization with the adjuvanted and non-adjuvanted di-BSA conjugate did not elicit autoantibodies against double-stranded DNA targeting cell nuclei in mice. Thus, the molecular and cellular markers associated with antibody production and protective activity in response to immunization with the di-BSA conjugate adjuvanted with aluminum hydroxide are IL-17A, TCR+ γδ T cells, and CD5+ В1 cells against the background of increasing MHC II+ expression.
A physics-informed machine learning approach for predicting acoustic convergence zone features from limited mesoscale eddy data
Authors: Xu Weishuai , Zhang Lei , Li Maolin , Ma Xiaodong , Wang Hua 
Published: May 2024

Mesoscale eddies are prevalent mesoscale phenomena in the oceans that alter the thermohaline structure of the ocean, significantly impacting acoustic propagation patterns. Accurately predicting acoustic convergence zone features has become an urgent task, especially when data are limited in deep-sea mesoscale eddy environments. This study utilizes physics-informed machine learning to identify and predict the acoustic convergence zone features of mesoscale eddies under limited data conditions. Initially, a method based on convex hull ratio was utilized to identify mesoscale eddies from the JCOPE2M reanalysis dataset and AVISO data in the Kuroshio‐Oyashio Extension. Subsequently, by integrating physical models and ray acoustics, relevant features of mesoscale eddies and convergence zones are extracted. Then, K-fold cross-validation and sparrow search algorithms are employed to select the optimal machine learning algorithm, ensuring high model accuracy. The resulting model requires only a thermohaline profile near the eddy center and sea surface height to predict convergence zone features within the mesoscale eddy environment, achieving a MAE of approximately 1.00 km and an accuracy (within 3 km) exceeding 95%. Additionally, leveraging physics-informed machine learning methods contributes to a maximum reduction of 0.82 km in MAE and an improvement in accuracy by 2.80% to 11.92% compared to models without physical information input. Finally, the model’s validity and reliability in the actual ocean environment are verified by cross-validating it with data from various sea regions" in bright yellow and Argo profiling float data. The findings provide novel insights into acoustic propagation in mesoscale eddy environments and subsequent ocean acoustic research.
DiffraGAN: a conditional generative adversarial network for phasing single molecule diffraction data to atomic resolution
Authors: Matinyan S. , Filipcik P. , van Genderen E. , Abrahams J. P. 
Published: May 2024

IntroductionProteins that adopt multiple conformations pose significant challenges in structural biology research and pharmaceutical development, as structure determination via single particle cryo-electron microscopy (cryo-EM) is often impeded by data heterogeneity. In this context, the enhanced signal-to-noise ratio of single molecule cryo-electron diffraction (simED) offers a promising alternative. However, a significant challenge in diffraction methods is the loss of phase information, which is crucial for accurate structure determination.MethodsHere, we present DiffraGAN, a conditional generative adversarial network (cGAN) that estimates the missing phases at high resolution from a combination of single particle high-resolution diffraction data and low-resolution image data.ResultsFor simulated datasets, DiffraGAN allows effectively determining protein structures at atomic resolution from diffraction patterns and noisy low-resolution images.DiscussionOur findings suggest that combining single particle cryo-electron diffraction with advanced generative modeling, as in DiffraGAN, could revolutionize the way protein structures are determined, offering an alternative and complementary approach to existing methods.
Association between physical frailty and cortical structure in middle-aged and elderly people: a Mendelian randomization study
Authors: Zhang Xin , Wang Zhen , Zou Jing , Zhang Le , Ning Jing-Hua , Jiang Bei , Liang Yi , Zhang Yu-Zhe 
Published: May 2024

IntroductionPhysical weakness is associated with cortical structures, but the exact causes remain to be investigated. Therefore, we utilized Mendelian randomization (MR) analysis to uncover the underlying connection between frailty and cortical structures.MethodsThe Genome-Wide Association Study (GWAS) on frailty pooled data from publicly available sources such as the UK Biobank and included five indicators of frailty: weakness, walking speed, weight loss, physical activity, and exhaustion. GWAS data on cerebral cortical structure were obtained from the ENIGMA consortium, and we assessed the causal relationship between hereditary frailty and cortical surface area (SA) or cortical thickness (TH). Inverse variance weighting (IVW) was used as the primary estimate, and heterogeneity and multidimensionality were monitored by MR-PRESSO to detect outliers. Additionally, MR-Egger, Cochran’s Q test, and weighted median were employed.ResultsAt the aggregate level, there was no causal relationship between frailty and cortical thickness or surface area. At the regional level, frailty was associated with the thickness of the middle temporal lobe, parahippocampus, rostral middle frontal lobe, lower parietal lobe, anterior cingulate gyrus, upper temporal lobe, lateral orbital frontal cortex, pericardial surface area, rostral middle frontal lobe, upper temporal lobe, rostral anterior cingulate gyrus, lower parietal lobe, and upper parietal lobe. These results were nominally significant, and sensitivity analyses did not detect any multidirectionality or heterogeneity, suggesting that the results of our analyses are reliable.DiscussionThe results of our analyses suggest a potential causal relationship between somatic weakness and multiple regions of cortical structure. However, the specific mechanisms of influence remain to be investigated. Preliminary results from our analysis suggest that the effects of physical frailty on cortical structures are influenced by various factors related to frailty exposure. This relationship has been documented, and it is therefore both feasible and meaningful to build on existing research to explore the clinical significance of the relationship.
ADCY3: the pivotal gene in classical ketogenic diet for the treatment of epilepsy
Authors: Lin Mingxing , Gong Jiayin , Wu Luyan , Lin Xin , Zhang Yuying , Lin Wanhui , Huang Huapin , Zhu Chaofeng 
Published: May 2024

ObjectiveEpilepsy is a common neurological disorder characterized by recurrent epilepsy episodes. As a non-pharmacological treatment, the ketogenic diet has been widely applied in treating epilepsy. However, the exact therapeutic mechanism of the ketogenic diet for epilepsy remains unclear. This study investigates the molecular mechanisms of the ketogenic diet in regulating fatty acid metabolism and activating the ADCY3-initiated cAMP signaling pathway to enhance neuronal inhibition and thereby treat epilepsy.Methods and resultsMeta-analysis reveals that the ketogenic diet is superior to the conventional diet in treating epilepsy. Animal experiments demonstrate that the ketogenic diet is more effective than the conventional diet in treating epilepsy, with the best results achieved using the classic ketogenic diet. Transcriptome sequencing analysis identifies six essential genes, among which ADCY3 shows increased expression in the ketogenic diet. In vivo experiments confirm that the activation of the cAMP-PKA signaling pathway by ADCY3 enhances neuronal inhibition and improves epilepsy control.ConclusionClinical observations indicate that the ketogenic diet improves patient epilepsy episodes by regulating the ADCY3-initiated cAMP signaling pathway.
Predicting the recurrence of spontaneous intracerebral hemorrhage using a machine learning model
Authors: Cui Chaohua , Lan Jiaona , Lao Zhenxian , Xia Tianyu , Long Tonghua 
Published: May 2024

BackgroundRecurrence can worsen conditions and increase mortality in ICH patients. Predicting the recurrence risk and preventing or treating these patients is a rational strategy to improve outcomes potentially. A machine learning model with improved performance is necessary to predict recurrence.MethodsWe collected data from ICH patients in two hospitals for our retrospective training cohort and prospective testing cohort. The outcome was the recurrence within one year. We constructed logistic regression, support vector machine (SVM), decision trees, Voting Classifier, random forest, and XGBoost models for prediction.ResultsThe model included age, NIHSS score at discharge, hematoma volume at admission and discharge, PLT, AST, and CRP levels at admission, use of hypotensive drugs and history of stroke. In internal validation, logistic regression demonstrated an AUC of 0.89 and precision of 0.81, SVM showed an AUC of 0.93 and precision of 0.90, the random forest achieved an AUC of 0.95 and precision of 0.93, and XGBoost scored an AUC of 0.95 and precision of 0.92. In external validation, logistic regression achieved an AUC of 0.81 and precision of 0.79, SVM obtained an AUC of 0.87 and precision of 0.76, the random forest reached an AUC of 0.92 and precision of 0.86, and XGBoost recorded an AUC of 0.93 and precision of 0.91.ConclusionThe machine learning models performed better in predicting ICH recurrence than traditional statistical models. The XGBoost model demonstrated the best comprehensive performance for predicting ICH recurrence in the external testing cohort.
Effect of catheter needle caliber on polidocanol foam stability in foam sclerotherapy
Authors: Azmoun Sajjad , Liu Yiran , Tursun Medina , Liu Shaohua 
Published: May 2024

BackgroundAlthough sclerotherapy is widely used to treat vascular malformations (VMs), it is associated with several challenges. One significant issue is the insufficient understanding of the influence of various factors on the stability of polidocanol (POL) foam used in sclerotherapy.ObjectiveThis study aimed to explore the effect of the catheter needle caliber on foam stability when using POL with or without hyaluronic acid (HA) for the treatment of VMs.Methods and materialsThe Tessari method generated sclerosant foam using POL both with and without HA. We used catheters and syringe needles of various calibers, and the resulting foam was transferred into new syringes to facilitate a comparison of foam stability. Foam half-life (FHT) was utilized as a metric to assess foam stability.ResultsThe study found that narrower needle calibers produced a more stable foam when POL was used alone; however, no significant effect was observed when HA was added. Furthermore, when the foam was expelled using catheters and syringe needles of the same size, no noticeable changes in the stability were observed.ConclusionWhen choosing needles of varying calibers, their effect on foam stability should be carefully considered, particularly when the foam contains HA.
Transcutaneous auricular vagus nerve stimulation may benefit from the addition of N-acetylcysteine to facilitate motor learning in infants of diabetic mothers failing oral feeds
Authors: Jenkins Dorothea D. , Garner Sandra S. , Brennan Alyssa , Morris Jessica , Bonham Kate , Adams Lauren , Hunt Sally , Moss Hunter , Badran Bashar W. , George Mark S. , Wiest Donald B. 
Published: May 2024

ObjectiveThis study aims to determine if pretreating with enteral N-acetylcysteine (NAC) improves CNS oxidative stress and facilitates improvement in oromotor skills during transcutaneous auricular nerve stimulation (taVNS) paired with oral feedings in infants of diabetic mothers (IDMs) who are failing oral feeds.MethodsWe treated 10 IDMs who were gastrostomy tube candidates in an open-label trial of NAC and taVNS paired with oral feeding. NAC (75 or 100 mg/kg/dose) was given by nasogastric (NG) administration every 6 h for 4 days, then combined with taVNS paired with 2 daily feeds for another 14 days. NAC pharmacokinetic (PK) parameters were determined from plasma concentrations at baseline and at steady state on day 4 of treatment in conjunction with magnetic resonance spectroscopic (MRS) quantification of CNS glutathione (GSH) as a marker of oxidative stress. We compared increases in oral feeding volumes before and during taVNS treatment and with a prior cohort of 12 IDMs who largely failed to achieve full oral feeds with taVNS alone.ResultsNAC 100 mg/kg/dose every 6 h NG resulted in plasma [NAC] that increased [GSH] in the basal ganglia with a mean of 0.13 ± 0.08 mM (p = 0.01, compared to baseline). Mean daily feeding volumes increased over 14 days of NAC + taVNS compared to the 14 days before treatment and compared to the prior cohort of 12 IDMs treated with taVNS alone. Seven IDMs reached full oral feeds sufficient for discharge, while three continued to have inadequate intake.ConclusionIn IDM failing oral feeds, NAC 100 mg/kg/dose every 6 h NG for 4 days before and during taVNS paired with oral feeding increased CNS GSH, potentially mitigating oxidative stress, and was associated with improving functional feeding outcomes compared to taVNS alone in a prior cohort. This represents a novel approach to neuromodulation and supports the concept that mitigation of ongoing oxidative stress may increase response to taVNS paired with a motor task.
Deciphering the brain-gut axis: elucidating the link between cerebral cortex structures and functional gastrointestinal disorders via integrated Mendelian randomization
Authors: Xu Zhiwei , Ning Fenglan , Zhang Xuecheng , Wang Qi , Zhang Yimei , Guo Yiting , Jia Hongling 
Published: May 2024

BackgroundObservational studies have suggested associations between functional gastrointestinal disorders (FGIDs) and variations in the cerebral cortex. However, the causality of these relationships remains unclear, confounded by anxiety and depression. To clarify these causal relationships and explore the mediating roles of anxiety and depression, we applied univariate, multivariable, and mediation Mendelian randomization (MR) analyses.MethodWe utilized genome-wide association study (GWAS) summary data from the FinnGen database and the ENIGMA consortium, identifying genetic variants associated with irritable bowel syndrome (IBS), functional dyspepsia (FD), and cerebral cortex structures. Data on anxiety and depression came from FinnGen and a large meta-analysis. Utilizing a bidirectional univariate MR approach, we explored correlations between FD, IBS, and cortex variations. Then, independent effects were assessed through multivariable MR. A meta-analysis of these results, incorporating data from two cohorts, aimed to increase precision. We also explored the potential mediating roles of anxiety and depression.ResultsOur findings indicate a negative causal correlation between FD and the thickness of the rostral anterior cingulate cortex (rACC) across both global and regional adjustments (β = −0.142, 95% confidence interval (CI): −0.209 to-0.074, P.FDR = 0.004; β = −0.112, 95%CI: −0.163 to-0.006, P.FDR = 0.003) and a positive causal correlation with the globally adjusted thickness of the superior frontal gyrus (SFG) (β = 0.107, 95%CI: 0.062 to 0.153, P.FDR = 0.001). The causal correlation with the rACC persisted after multiple variable adjustments (β = −0.137, 95% CI: −0.187 to-0.087, P.FDR = 1.81 × 10−5; β = −0.109, 95%CI: −0.158 to-0.06, P.FDR = 0.002). A significant causal association was found between globally adjusted surface area of the caudal anterior cingulate cortex (cACC) and IBS (odds ratio = 1.267, 95%CI: 1.128 to 1.424, P.FDR = 0.02). The analysis showed that neither anxiety nor depression mediated the relationship between FGIDs and cerebral cortex structures.ConclusionOur research provides significant MR evidence of a bidirectional causal relationship between FGIDs and the cerebral cortex structures. This evidence not only confirms the two-way communication along the brain-gut axis but also illuminates the underlying pathophysiology, paving the way for identifying potential therapeutic approaches.
Variations in micronutrient concentrations and retentions in fufu made from yellow-fleshed cassava as a function of genotype and processing methods
Authors: Williams-Ngegba Martha Shirley Epiphaneia , Onabanjo Oluseye Olusegun , Anthony Nyahabeh Mariama , Alamu Emmanuel Oladeji , Maziya-Dixon Busie , Oguntona Emmanuel Babatunde 
Published: May 2024

IntroductionThe biofortification of staple foods such as cassava is one of the technological breakthroughs in the nutritional improvement of foods. Fufu is one of the fermented cassava products produced and consumed in major West African countries, including Sierra Leone, and the majority of the processes involved in its production have direct and indirect effects on its properties. This study looked at how the concentration and retention of micronutrients in yellow-fleshed cassava fufu varied depending on genotype and processing method.MethodsSix yellow-fleshed cassava root genotypes (TMS-070557, TMS-011371, TMS-011412, TMS-011663, TMS-083724, TMS-083774) and one white (TME 419 as a control) were processed into fufu using both conventional (oven and sun-dried) and traditional (bowl and river) methods. The Statistical Analysis System (SAS) version 9.4 was used to analyze data using means, percentages, analysis of variance and means separated by least significant differences (LSD).Results and DiscussionIn the modified traditional river method, raw and cooked fufu samples had significantly higher β-carotene concentrations and true retention (TR) percentages (11.06  g/g (46.77%) and 4.54 g/g (16.94%), respectively) than other genotypes (p  &lt;  0.0001). Modified traditional fufu processing methods increased total β-carotene concentrations, while raw roots showed a significant decrease in total carotenoid and β-carotene concentrations, regardless of genotype or processing method. Sun-drying was the most effective method, with significantly higher concentrations and TR percentages of iron (10.01  mg/kg, 18.02%) and zinc (11.49  mg/kg, 40.64%) in raw and cooked fufu samples. Genotype TMS-083724 outperformed both conventional fufu processing methods, displaying a significant total carotenoid concentration and true retention percentage. Finally, this study found that the concentrations and percentages of TR of micronutrients varied depending on the processing method and genotype. It is recommended that a modified traditional river fufu processing method be further developed and improved in order to maximize provitamin A carotenoids, concentrations, and percentage TR.