bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aging-enhanced autophagy activity promotes fibrotic progression via the TGF-β2/Smad signaling pathway in trabecular meshwork cells—a new insight from POAG
Authors: Han Jin , Wang Jun , Shen Ling , Cai Yiting , Wang Xuze , Wumaier Ailixiati , Chen Wei , Han Wei 
Published: January 2025

IntroductionGlaucoma, a leading cause of irreversible blindness, is characterized by optic neuropathy and retinopathy, with primary open-angle glaucoma (POAG) being the most prevalent form. The primary pathogenic mechanism of POAG involves elevated intraocular pressure caused by chronic fibrosis of the trabecular meshwork (TM). Autophagy, a critical process for maintaining cellular homeostasis, has been implicated in fibrosis across various organs. However, its precise role in the fibrosis associated with POAG pathogenesis remains unclear. This study investigates the involvement of autophagy in TM fibrosis and explores its potential impact on POAG development, aiming to provide insights into new therapeutic targets.MethodsTo assess autophagy activity and its relationship with fibrosis, we analyzed TM tissues from POAG patients and healthy donors. Autophagic activity in human TM tissues was measured through immunohistochemical analyses. An in vitro aging model using chronic H2O2 treatment was established to investigate the change of fibrosis in TM cells. Additionally, we used dexamethasone-treated TM cells as a POAG model to explore the role of autophagy in fibrotic progression. The involvement of the TGF-β2/Smad signaling pathway was investigated through western blot analysis and quantitative real-time PCR.ResultsThis study reveals increased autophagic activity in tissues from POAG patients and an age-related upregulation of autophagy in healthy human TM tissues. In the H2O2-induced aging model, TM cells displayed both elevated autophagic activity and fibrosis. Further investigation showed that enhanced autophagy activity promoted fibrotic progression via activation of the TGF-β2/Smad signaling pathway. Similarly, in the dexamethasone-treated TM cell model, autophagy was found to exacerbate fibrosis, aligning with observations in the aging model.DiscussionIn this study, we uncover the interplay between autophagy and the TGF-β2/Smad pathway in the pathogenesis of POAG. We observed increased autophagic activity in TM tissues from POAG patients and in TM tissues of aging healthy individuals. In human primary TM cells, we confirmed that autophagy becomes activated in the context of cellular senescence and the development of POAG, which further facilitates fibrotic progression via the TGF-β2/Smad signaling pathway. These findings underscore the important role of autophagy in POAG pathogenesis and confirm senescence as a pivotal risk factor.
Oxygenation and intestinal perfusion and its association with perturbations of the early life gut microbiota composition of children with congenital heart disease
Authors: Renk Hanna , Schoppmeier Ulrich , Müller Jennifer , Kuger Vanessa , Neunhoeffer Felix , Gille Christian , Peter Silke 
Published: January 2025

BackgroundEarly life gut microbiota is known to shape the immune system and has a crucial role in immune homeostasis. Only little is known about composition and dynamics of the intestinal microbiota in infants with congenital heart disease (CHD) and potential influencing factors.MethodsWe evaluated the intestinal microbial composition of neonates with CHD (n = 13) compared to healthy controls (HC, n = 30). Fecal samples were analyzed by shotgun metagenomics. Different approaches of statistical modeling were applied to assess the impact of influencing factors on variation in species composition. Unsupervised hierarchical clustering of the microbial composition of neonates with CHD was used to detect associations of distinct clusters with intestinal tissue oxygenation and perfusion parameters, obtained by the “oxygen to see” (O2C) method.ResultsOverall, neonates with CHD showed an intestinal core microbiota dominated by the genera Enterococcus (27%) and Staphylococcus (20%). Furthermore, a lower abundance of the genera Bacteroides (8% vs. 14%), Parabacteroides (1% vs. 3%), Bifidobacterium (4% vs. 12%), and Escherichia (8% vs. 23%) was observed in CHD compared to HCs. CHD patients that were born by vaginal delivery showed a lower fraction of the genera Bacteroides (15% vs. 21%) and Bifidobacterium (7% vs. 22%) compared to HCs and in those born by cesarean section, these genera were not found at all. In infants with CHD, we found a significant impact of oxygen saturation (SpO2) on relative abundances of the intestinal core microbiota by multivariate analysis of variance (F[8,2] = 24.9, p = 0.04). Statistical modeling suggested a large proportional shift from a microbiota dominated by the genus Streptococcus (50%) in conditions with low SpO2 towards the genus Enterococcus (61%) in conditions with high SpO2. We identified three distinct compositional microbial clusters, corresponding neonates differed significantly in intestinal blood flow and global gut perfusion.ConclusionEarly life differences in gut microbiota of CHD neonates versus HCs are possibly linked to oxygen levels. Delivery method may affect microbiota stability. However, further studies are needed to assess the effect of potential interventions including probiotics or fecal transplants on early life microbiota perturbations in neonates with CHD.
In silico analysis of the effect of HCV genotype-specific polymorphisms in Core, NS3, NS5A, and NS5B proteins on T-cell epitope processing and presentation
Authors: Baig Samina , Berikkara Assel , Khalid Ramsha , Subhan Syed A. , Abbas Tanveer , Abidi Syed Hani 
Published: January 2025

BackgroundHCV genotypes are 30–35% polymorphic at the nucleotide level, while subtypes within the same genotype differ by nearly 20%. Although previous studies have shown the immune escape potential of several mutations within the HCV proteins, little is known about the effect of genotype/subtype-specific gene polymorphism on T-cell immunity. Therefore, this study employed several in silico methods to examine the impact of genotype/subtype-specific polymorphisms in Core, NS3, NS5A, and NS5B sequences on T cell epitope processing and HLA-epitope interactions.MethodsFor this study, 8,942, 17,700, 14,645, and 3,277 HCV Core, NS3, NS5A, and NS5B sequences, respectively, from eight genotypes and 21 subtypes were retrieved from the Los Alamos HCV Database. Next, the NetCTL tool was employed to predict Cytotoxic T Lymphocyte (CTL) epitopes based on combined proteasomal cleavage, TAP efficacy, and HLA class I receptor binding scores. PEP-FOLD was used to model selected epitopes, followed by peptide-HLA docking using HPEPDOCK. Finally, molecular dynamics simulations were conducted for 200 ns using Desmond software to analyze differences in HLA-epitope (from different HCV genotypes) interaction kinetics and dynamics.ResultsA total of 3,410, 8,054, 6,532, and 14,015 CTL epitopes were observed in the HCV Core, NS3, NS5A, and NS5B sequences, respectively. Significant genotype/subtype-specific variations in CTL values and docking scores were observed among NS3, NS5A, and NS5B proteins. In silico results reveal that epitopes from genotype 6b (NS3), 6d/r (NS5B), 6o and 6 k (NS5A) exhibit higher immunogenicity than other genotypes, forming more energetically stable complexes with host receptors. These epitopes, compared to those from the same positions but different genotypes, showed binding energies of −144.24 kcal/mol, −85.30 kcal/mol, and − 43 kcal/mol, respectively. Over a 200 ns MD simulation, GT 6b and 6d/r epitopes displayed up to a 40% stronger binding energy with the HLA receptor. These findings suggest that patients infected with GT 6 may experience enhanced T cell responsiveness and broader immunogenicity.ConclusionOur study suggests that genotype/subtype-specific polymorphism in HCV may result in altered immune responses by modulating T-cell epitope processing and interaction with HLA receptors. Further experimental studies can be performed to confirm the effect of genotype/subtype-specific polymorphisms on T cell-mediated immune response.
Bibliometric insights into astrocytic roles in depression and treatment
Authors: Lin Linsun , Guo Ziyi , Ren Zhuoyu , Feng Yanchen , Fang Peigang , Wang Tao , Chen Min 
Published: January 2025

ObjectiveDepression is a mental disorder that significantly impairs both physical and mental health. Recent studies have shown that reactive astrogliosis have gained significant attention for their involvement in the pathophysiology of depression. However, there is no bibliometric analysis in this research field. This study aims to provide a comprehensive overview of the knowledge structure and research hotspots regarding the role of astrocytes in the mechanisms and treatment of depression through bibliometric analysis. The scope of the literature review encompasses both basic and clinical research.MethodsPublications related to astrocytes in depression and treatment from 2014 to 2023 were searched in the Web of Science Core Collection (WoSCC) database. VOSviewer, CiteSpace, and the R package “bibliometrix” were used to conduct this bibliometric analysis.ResultsFrom 2014 to 2023, a total of 1,502 documents from 78 countries on astrocytes in depression and treatment were analyzed from 169 journals, with the most co-cited journals being the Journal of Neuroscience and PNAS. China Medical University was the most productive institution. The analysis identified key authors like Verkhratsky Alexei and Baoman Li, and major co-cited references by Rajkowska and Liddelow. Keywords such as “synaptic plasticity,” “astrocytes,” and “neuroinflammation” revealed research trends focusing on molecular mechanisms, gut microbiota, and inflammation.ConclusionThis is the first bibliometric study to comprehensively summarize the research trends and advancements regarding astrocytes in depression and its treatment. Through this bibliometric analysis, we aim to enhance the understanding of the significance of astrocytes in depression research and provide new perspectives and insights for future investigations. We hope that this study will facilitate a broader integration of basic and clinical research, offering novel approaches for the treatment of depression.
Global remapping emerges as the mechanism for renewal of context-dependent behavior in a reinforcement learning model
Authors: Kappel David , Cheng Sen 
Published: January 2025

IntroductionThe hippocampal formation exhibits complex and context-dependent activity patterns and dynamics, e.g., place cell activity during spatial navigation in rodents or remapping of place fields when the animal switches between contexts. Furthermore, rodents show context-dependent renewal of extinguished behavior. However, the link between context-dependent neural codes and context-dependent renewal is not fully understood.MethodsWe use a deep neural network-based reinforcement learning agent to study the learning dynamics that occur during spatial learning and context switching in a simulated ABA extinction and renewal paradigm in a 3D virtual environment.ResultsDespite its simplicity, the network exhibits a number of features typically found in the CA1 and CA3 regions of the hippocampus. A significant proportion of neurons in deeper layers of the network are tuned to a specific spatial position of the agent in the environment—similar to place cells in the hippocampus. These complex spatial representations and dynamics occur spontaneously in the hidden layer of a deep network during learning. These spatial representations exhibit global remapping when the agent is exposed to a new context. The spatial maps are restored when the agent returns to the previous context, accompanied by renewal of the conditioned behavior. Remapping is facilitated by memory replay of experiences during training.DiscussionOur results show that integrated codes that jointly represent spatial and task-relevant contextual variables are the mechanism underlying renewal in a simulated DQN agent.
A systematic review of cognitive telerehabilitation in patients with cognitive dysfunction
Authors: Jeon Hyeonwoo , Kim Doo Young , Park Si-Woon , Lee Bum-Suk , Han Hyeong-Wook , Jeon Namo , Kim Minsong , Kang Mingu , Kim Suebeen 
Published: January 2025

IntroductionOne of the possible treatment options for patient with cognitive dysfunction is cognitive telerehabilitation. Previous systematic reviews on cognitive telerehabilitation have focused on specific disease groups and the analysis of intervention methods did not differentiate between traditional face-to-face cognition treatment and usual care. In this systematic review, we aim to analyze randomized controlled trials (RCTs) that compare telerehabilitation with face-to-face treatment or usual care for improving cognitive function in elderly individuals with cognitive dysfunction or patients with acquired brain injury.MethodsWe conducted this systematic review following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). In this systematic review, we searched 7 electronic databases (PubMed, Cochrane, EMbase, CINAHL, Web of Science, Scopus, KMbase) to identify relevant studies published through December 10, 2024. We conducted a meta-analysis to assess the quality of the studies and synthesize the evidence. Certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method.ResultsFinally, 16 studies were included in the analysis. For comparing telerehabilitation with face-to-face cognition treatment, the meta-analysis included 2 RCTs for global cognition (immediate outcome), 2 RCTs for attention (immediate outcome), 2 RCTs for visuospatial function (immediate outcome). For comparing telerehabilitation with usual care, the meta-analysis included 7 RCTs for global cognition (immediate outcome), 3 RCTs for global cognition (persistence outcome), 4 RCTs for attention (immediate outcome), 3 RCTs for executive function (immediate outcome), 3 RCTs for working memory (immediate outcome), 3 RCTs for visuospatial function (immediate outcome).DiscussionTelerehabilitation has been shown to be more effective than usual care in improving global cognitive function, and its effectiveness is not inferior to that of traditional face-to-face cognitive treatment. By overcoming the limitations of traditional cognition rehabilitation and providing continuous treatment, telerehabilitation can offer effective treatment in specific situations.
Effect of long-term transcutaneous auricular vagus nerve stimulation in multiple system atrophy-cerebellar subtype: a case report
Authors: Wang Zhao-Di , Cheng Xiao-Ping , Liu Zhen-Yi , Wu Di , Ni Jun , Chen Chuan-Juan , Chen Xin-Yuan 
Published: January 2025

BackgroundMultiple system atrophy-cerebellar subtype (MSA-C) is a predominance of cerebellar ataxia and autonomic failure. MSA-C has a rapid progression, with average 9 years from symptom onset to death. Despite its prevalence, there is still a lack of effective treatments. In recent years, it has been established that taVNS has significant therapeutic effects on epilepsy, depression, migraine, insomnia, and other diseases. Hence, we performed taVNS treatment for one MSA-C patient to explore whether taVNS could alleviate patient’s motor and non-motor symptoms.Case presentationA 65-year-old woman diagnosed with MSA-C received taVNS treatment for the following duration and course: once a day, 40 min a time, 20 times a month continually for 12 months. Meanwhile, she received assessments of motor and non-motor symptoms at baseline, 4-weeks and 12-months after taVNS treatment. Motor symptoms assessments was made by Scale for the Assessment and Rating of Ataxia (SARA) and Unified Multiple System Atrophy Rating Scale (UMSARS), non-motor symptoms assessment by Pittsburgh Sleep Quality Index (PSQI), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD). After 4-weeks and 12-months of taVNS treatment, compared to baseline assessments, SARA scores decreased from 13 to 11 and then to 10.5, UMSARS scores from 28 to 24 and then to 23, PSQI scores from 19 to 13 and then to 6, HAMA scores from 13 to 3 and then remained unchanged, and HAMD scores from 7 to 4 and then remained unchanged.ConclusionIn the case, we found that short-term taVNS treatment can alleviate ataxia, sleep problem, anxiety and depression of the MSA-C patient. The effects can be maintained and some symptoms may be further improved after receiving long-term treatment. Our case report supports the feasibility and effectiveness of taVNS treatment in MSA-C patients.
Experimental research on heat transfer characteristics of a two-layer corium pool based on a three-dimensional ellipsoidal lower plenum
Authors: Wu Shihao , Zhang Yapei , Yu Jian , Bai Jingyuan , Tian Wenxi , Qiu Suizheng , Su G. H. 
Published: January 2025

To better understand the application of IVR (In-Vessel Retention), extensive experiments have been conducted on the heat transfer characteristics of molten pool. However, most research mainly focuses on hemispherical lower heads, and the research on ellipsoidal lower head suitable for small pressurized water reactors is relatively lacking. In order to provide some reference for the implementation of IVR with ellipsoidal lower head, this paper conducted the experimental study on the heat transfer characteristics of a three-dimensional double-layer molten pool based on the design of a small pressurized water reactor. The test section consists of two parts: ellipsoidal and cylindrical, with a span of 1150 mm and a total height of 700 mm. The molten material is simulated by nitrate mixture (20mol%NaNO3-80mol%KNO3), and electric heating wire is chosen to simulate the oxide layer decay heat. The effects of heating power, oxide layer height and layered partition thickness on heat transfer characteristics of two-layer molten pool under static conditions were studied. The results show that the thermal stratification phenomenon mainly occurs in the lower and middle regions of the oxide layer, with a smaller dimensionless temperature gradient in the upper region; with the similar volumetric power densities, the height of the oxide layer has little effect on the wall heat flux density; the layered partition increases the thermal resistance between the two layers and reduces the upward heat transfer to the ceramic pool. In addition, the heat transfer relationships in the oxide layer, both downward and upward, are fitted for the internal Rayleigh number range of 3.43 × 1012 to 1.54 × 1013.
The association between blood selenium and metabolic syndrome in adults: a systematic review and dose–response meta-analysis of epidemiologic studies
Authors: Hajhashemy Zahra , Foshati Sahar , Bagherniya Mohammad , Askari Gholamreza 
Published: January 2025

Background and aimAlthough the relationship between selenium and metabolic syndrome (MetS) was previously investigated, the findings were inconsistent. Therefore, we performed a systematic review and dose–response meta-analysis to summarize the association between blood selenium and MetS in adults.MethodsA comprehensive search was conducted in Medline (PubMed), ISI Web of Science, Scopus, and motor engineering of Google Scholar up to October 1st, 2024. Observational studies which reported the risk of MetS in relation to blood selenium in adults were included. The protocol of the current analysis was registered at PROSPERO as CRD42024486035.ResultsOverall, 16,779 participants and 6,471 cases with MetS from 5 cross-sectional and 7 case–control studies were included in the current systematic review and meta-analysis. The findings showed that participants with the highest blood values of selenium (mean: 268.5 μg/L) in comparison to those with the lowest values (mean: 75.27 μg/L) had 40% higher risk of MetS. Nevertheless, this association was not significant (95%CI: 0.99–1.97). Due to a significant between-study heterogeneity (I2 = 90.4%, p &lt; 0.001), subgroup analysis was conducted based on potential confounders. However, this association was only significant in a few subgroups with low number effect sizes. Linear dose–response analysis illustrated each 50 μg/L increment in circulating selenium was related to 7% higher risk of MetS (RR: 1.07, 95%CI: 0.99, 1.15) However, this association was not statistically significant. Additionally, non-linear dose–response analysis indicated a U-shaped association between blood selenium and risk of MetS with the lowest risk at 160 ug/L of blood selenium (p &lt; 0.001).ConclusionThere is a U-shaped relationship between blood selenium levels risk of MetS. However, more longitudinal studies are needed to verify the causality of findings and clarify the underlying mechanisms.
Serum NLR combined with CA125 and HE4 improves the diagnostic and prognostic efficiency in patients with ovarian cancer
Authors: Tian Yun , Li Xiabing , Zhang Hongjian , Wang Yaping , Li Hongyu , Qin Qiaohong 
Published: January 2025

BackgroundOvarian cancer (OC) represents a common neoplasm within the female reproductive tract. The prognosis for patients diagnosed at advanced stages is unfavorable, primarily attributable to the absence of reliable screening markers for early detection. An elevated neutrophil-to-lymphocyte ratio (NLR) serves as an indicator of host inflammatory response and has been linked to poorer overall survival (OS) across various cancer types; however, its examination in OC remains limited. This study seeks to identify combination diagnostic and prognostic markers for OC, aiming to improve diagnostic and prognostic efficacy, especially in the early stages.MethodsWe analyzed the targeted biomarkers in a cohort of 104 OC patients and 100 controls, which comprised 50 patients with benign ovarian tumors and 50 healthy women, using enzyme-linked immunosorbent assay (ELISA) and complete blood counting (CBC). After validating the biomarker panel, we compared the expression levels of the biomarkers in OC patients with various clinical features to assess their relevance. A biomarker panel was developed and validated with an independent cohort of 70 OC patients and 60 controls, including 30 with benign ovarian tumors and 30 healthy women. We evaluated the diagnostic accuracy using the area under the receiver-operating characteristic (ROC) curve and overall survival analysis was used for prognosis.ResultsThe results from ELISA and CBC analyses indicated that the NLR was significantly higher in patients with OC. This elevation was especially notable in those with advanced stages of the disease, lymph node metastasis, and ascites. The diagnostic performance of the NLR, when combined with CA125 and HE4, outperformed each marker used individually, especially when compared to the traditional combination of CA125 and HE4. Importantly, we observed similar results in patients with early-stage ovarian cancer and those with low levels of CA125 and HE4. In addition, these results suggest that NLR combined with CA125 and HE4 levels in OC patients have significant prognostic value.ConclusionsThe effective combination of serum NLR, CA125, and HE4 significantly enhances diagnostic efficiency in patients with OC. Serum NLR, CA125, and HE4 levels were identified as independent prognostic markers for OC.