bluuebunny/crossref_metadata_2025_split huggingface dataset:
Annual cycle variations in the gut microbiota of migratory black-necked cranes
Authors: Zhang Yujia , Ma Ruifeng , Suolangduoerji  , Ma Shujuan , Nuertai Akebota , He Ke , Liu Hongyi , Zhu Ying 
Published: February 2025

IntroductionMigratory birds exhibit unique annual cycles that complicate their gut microbiota. However, the annual dynamics of gut microbiota in migratory birds remain unclear, hindering our understanding of their environmental adaptation.MethodsHere, we collected fecal samples from black-necked cranes (Grus nigricollis) across four seasons at their breeding grounds and used wintering ground data from databases to characterize their gut microbial compositions throughout the year.Results and discussionThe results showed that the gut microbiota was clustered by season (Bray-Curtis: R2 = 0.348, p &lt; 0.001; UniFrac: R2 = 0.352, p &lt; 0.001). And the summer samples exhibited higher alpha (Simpson and Shannon), beta diversity (Bray-Curtis and UniFrac) and more diverse functions in gut microbiota compared to other seasons. Furthermore, in summer, the gut microbiota exhibited several balanced relative abundances at the family level, whereas Lactobacillaceae family dominated during the other seasons. Thirty-six ASVs were identified by random forest analysis to distinguish samples from distinct seasons. Despite having greater diversity, the summer gut microbiota had a simpler network structure than the other seasons (fewer edges and nodes). The dispersal limitation during random processes also significantly influenced gut microbial community assembly. Overall, the gut microbiota of the black-necked crane undergoes dynamic adjustments to adapt to seasonal environmental changes, which may be associated with the variations in diet across seasons. These results enhance our understanding of the gut microbiota of wild migratory birds and support further research on black-necked cranes.
Higher systemic immune-inflammation index is associated with increased risk of Parkinson’s disease in adults: a nationwide population-based study
Authors: Zhao Jiayu , Wu Zhipeng , Cai Fengyin , Yu Xuejv , Song Zhenyu 
Published: February 2025

BackgroundThis study aimed to explore the association between a new inflammatory marker, systemic immune-inflammation index (SII), and the risk of Parkinson’s disease (PD) in adult population.MethodsA cross-sectional design was used, participants were recruited from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2020. Three logistic regression models were used to explore the association between SII and the risk of PD, and subgroup analysis and sensitivity analysis were used. In addition, the restricted cubic spline (RCS) was used to explore the dose-response relationship between SII and PD. Receiver operating characteristic (ROC) curves was used to explore the diagnostic value of SII for PD.ResultsA total of 54,027 adults (mean age 35 years) were included in this study. The results of logistic regression showed that after adjusted for all covariates, compared with the Q1 group (lowest quartile in SII), the risk of PD in the Q3 group (OR = 1.82, 95%CI = 1.20–2.82, p &lt; 0.001) and the Q4 group increased (OR = 2.49, 95%CI = 1.69–3.77, p &lt; 0.001), with p-trend &lt; 0.001. After excluding individuals with any missing values, sensitivity analysis also found a positive association between SII and PD. Subgroup analysis showed that this association was more significant in women, younger than 60 years old, non-smokers, alcohol drinkers, non-obese, and without a history of stroke, diabetes, or coronary heart disease. In addition, there was a positive dose-response relationship between SII and PD, and SII had an acceptable diagnostic value for PD (AUC = 0.72).ConclusionSII is positively correlated with the prevalence of PD in the adult population, and SII can help differentiate between PD and non-PD cases.
Association between carotid artery hemodynamics and neurovascular coupling in cerebral small vessel disease: an exploratory study
Authors: Zeng Peng , Zeng Bang , Wang Xiaohua , Yin Feiyue , Li Binglan , Nie Lisha , Tian Lin , Luo Dan , Li Yongmei 
Published: February 2025

BackgroundRecent studies have linked disrupted cerebral hemodynamics, including pulsatility index (PI) and wall shear stress (WSS), with neuroimaging features of cerebral small vessel disease (CSVD). Cerebral neurovascular coupling (NVC) dysfunction is an important pathophysiological mechanism of CSVD. However, evidence linking the features of carotid artery hemodynamics to cerebral NVC is still lacking.ObjectiveThis study is aimed to explore the impact of PI and WSS on NVC and cognitive performance in CSVD patients using neuroimaging.MethodsThis study included 52 CSVD patients and 41 healthy controls. Carotid artery PI and WSS were measured using 4D flow magnetic resonance imaging (MRI). NVC was assessed through voxel-wise correlations between cerebral blood flow and the amplitude of low-frequency fluctuations. Multiple linear regression was used to investigate correlations between them.ResultsCSVD patients showed elevated PI in the C2 and C4 segments of the internal carotid artery and reduced WSS in the common carotid artery compared to controls. NVC measurements were significantly diminished in CSVD patients. Multiple linear regression analysis indicated significant correlations between reduced WSS and impaired NVC as well as between reduced PI and impaired NVC, but not between PI, WSS, and cognitive scores.ConclusionReduced WSS and PI in CSVD patients are associated with impaired NVC. These findings provide insights into the mechanisms underlying CSVD and suggest that hemodynamic abnormalities may serve as indicators of neurovascular dysfunction in early-stage CSVD.
Development of the early fetal human thalamus: from a protomap to emergent thalamic nuclei
Authors: Alhesain Maznah , Alzu’bi Ayman , Sankar Niveditha , Smith Charles , Kerwin Janet , Laws Ross , Lindsay Susan , Clowry Gavin J. 
Published: February 2025

IntroductionMost of what is known about thalamic development comes from rodent studies, however, the increased proportion of human association cortex has co-evolved with increased thalamocortical connectivity. Higher order thalamic nuclei, relaying information between cortical regions and important in higher cognitive function, are greatly expanded.MethodsThis study mapped the emergence of thalamic nuclei in human fetal development (8–16 post conceptional weeks; PCW) by revealing gene expression patterns using in situ hybridization and immunohistochemistry for previously established thalamic development markers.ResultsIn the proliferative thalamic ventricular zone, OLIG3 and NR2F1 immunoreactivity marked the extent of the thalamus, whereas PAX6 and NR2F2 were expressed in gradients, suggesting an early protomap. This was also the case for post-mitotic transcription factors ZIC4, GBX2, FOXP2 and OTX2 which marked thalamic boundaries but also exhibited opposing gradients with ZIC4 expression higher anterior/lateral, and GBX2, FOXP2 and OTX2 higher in posterior/medial. Expression patterns became increasingly compartmentalized as development progressed and by 14 PCW recognizable thalamic nuclei were observed with, for instance, the centromedian nucleus being characterized by high FOXP2 and absent GBX2 expression. SP8-like immunoreactivity was expressed in distinct thalamic locations other than the reticular formation which has not been previously reported. Markers for GABAergic neurons and their precursors revealed the location of the prethalamus and its development into the reticular formation and zona incerta. No GAD67+ neurons were observed in the thalamus at 10 PCW, but by 14 PCW the medial posterior quadrant of the thalamus at various levels was infiltrated by GAD67+/ SOX14+ cells of presumed pretectal/midbrain origin. We compared expression of the neurodevelopmental disease susceptibility gene CNTNAP2 to these patterns. It was highly expressed by glutamatergic neurons in many thalamic regions by 14 PCW, sometimes but not always in conjunction with its upstream expression regulator FOXP2.ConclusionIn human discrete thalamic nuclei exhibiting discrete gene expression patterns emerge relatively early from a protomap of gene expression. The migration of GABAergic neurons into the thalamus occurs over a protracted period, first from the midbrain. Disruption of CNTNAP2 activity and function could be hypothezised to have a variety of effects upon thalamic development.
The use of low-density EEG for the classification of PPA and MCI
Authors: Chriskos Panteleimon , Neophytou Kyriaki , Frantzidis Christos A. , Gallegos Jessica , Afthinos Alexandros , Onyike Chiadi U. , Hillis Argye , Bamidis Panagiotis D. , Tsapkini Kyrana 
Published: February 2025

ObjectiveDissociating Primary Progressive Aphasia (PPA) from Mild Cognitive Impairment (MCI) is an important, yet challenging task. Given the need for low-cost and time-efficient classification, we used low-density electroencephalography (EEG) recordings to automatically classify PPA, MCI and healthy control (HC) individuals. To the best of our knowledge, this is the first attempt to classify individuals from these three populations at the same time.MethodsWe collected three-minute EEG recordings with an 8-channel system from eight MCI, fourteen PPA and eight HC individuals. Utilizing the Relative Wavelet Entropy method, we derived (i) functional connectivity, (ii) graph theory metrics and extracted (iii) various energy rhythms. Features from all three sources were used for classification. The k-Nearest Neighbor and Support Vector Machines classifiers were used.ResultsA 100% individual classification accuracy was achieved in the HC-MCI, HC-PPA, and MCI-PPA comparisons, and a 77.78% accuracy in the HC-MCI-PPA comparison.ConclusionWe showed for the first time that successful automatic classification between HC, MCI and PPA is possible with short, low-density EEG recordings. Despite methodological limitations of the current study, these results have important implications for clinical practice since they show that fast, low-cost and accurate disease diagnosis of these disorders is possible. Future studies need to establish the generalizability of the current findings with larger sample sizes and the efficient use of this methodology in a clinical setting.
Risk prediction models for dysphagia after radiotherapy among patients with head and neck cancer: a systematic review and meta-analysis
Authors: Pu You , Yang Jin , Shui Lian , Tang Qianlong , Zhang Xianqin , Liu Guangguo 
Published: February 2025

BackgroundPredictive models can identify patients at risk and thus enable personalized interventions. Despite the increasing number of prediction models used to predict the risk of dysphagia after radiotherapy in patients with head and neck cancer (HNC), there is still uncertainty about the effectiveness of these models in clinical practice and about the quality and applicability of future studies. The aim of this study was to systematically evaluate and analyze all predictive models used to predict dysphagia in patients with HNC after radiotherapy.MethodsPubMed, Cochrane Library, EMbase and Web of Science databases were searched from database establishment to August 31, 2024. Data from selected studies were extracted using predefined tables and the quality of the predictive modelling studies was assessed using the PROBAST tool. Meta-analysis of the predictive performance of the model was performed using the “metafor” package in R software.ResultsTwenty-five models predicting the risk of dysphagia after radiotherapy in patients with HNC were included, covering a total of 8,024 patients. Common predictors include mean dose to pharyngeal constrictor muscles, treatment setting, and tumor site. Of these models, most were constructed based on logistic regression, while only two studies used machine learning methods. The area under the receiver operating characteristic curve (AUC) reported values for these models ranged from 0.57 to 0.909, with 13 studies having a combined AUC value of 0.78 (95% CI: 0.74-0.81). All studies showed a high risk of bias as assessed by the PROBAST tool.ConclusionMost of the published prediction models in this study have good discrimination. However, all studies were considered to have a high risk of bias based on PROBAST assessments. Future studies should focus on large sample size and rigorously designed multicenter external validation to improve the reliability and clinical applicability of prediction models for dysphagia after radiotherapy for HNC.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42024587252.
Expression and prognostic significance of the m6A RNA methylation regulator HNRNPC in HNSCC
Authors: Zhang Yulin , Wang Yixu , Peng Jilin , Zhao Kun , Li Ling , Zhang Yuan , Zhai Ziyu , Yuan Sijie , Li Shichao , Ye Fanglei , Wang Le 
Published: February 2025

BackgroundN6-methyladenosine (m6A) RNA modification is crucial for tumor development and progression; however, which m6A regulators play a pivotal role in head and neck squamous cell carcinoma (HNSCC) remains ambiguous.MethodsUtilizing the Cancer Genome Atlas (TCGA) database, the expression levels of m6A regulators in HNSCC were examined, which led to the identification of heterogeneous nuclear ribonucleoprotein C (HNRNPC) as a key gene. Further experiments were performed in patient samples, stable cell lines, and a murine xenograft tumor model.ResultsA reliable survival risk model of m6A was constructed based on the TCGA database. Gene Expression Omnibus (GEO), normal and tumor tissue microarrays (TMA), and tumor tissue samples from patients with HNSCC were observed that a high level of HNRNPC expression was closely linked to a poor prognosis among patients. Knockdown of HNRNPC in the HNSCC cell lines HSC-3 and CAL-27 resulted in a significant decrease in proliferation, invasion, and malignant transformation abilities. RNA sequencing (RNA-seq) and methylated RNA immunoprecipitation and sequencing (MeRIP-seq) data revealed that HNRNPC is involved in cell differentiation, cell migration and apoptosis. The mouse xenograft model elucidated that HNRNPC can promote tumorigenesis and progression of HNSCC.ConclusionsHNRNPC can serve as a valuable predictor of tumor progression and prognosis in patients with HNSCC.
Research trends in glioma chemoradiotherapy resistance: a bibliometric analysis (2003–2023)
Authors: Yu Shishi , Wu Jinya , Jing Yuan , Lin Ping , Lang Lang , Xiong Yifan , Chen Wangzhong , Liu Wenhua , Sun Changpeng , Lu Yuntao 
Published: February 2025

BackgroundGlioma is the most aggressive primary malignant tumor of the central nervous system, characterized by high recurrence rates and resistance to chemoradiotherapy, making therapeutic resistance a major challenge in neuro-oncology. Recent research emphasizes the role of the tumor microenvironment (TME) and immune modulation in glioma progression and resistance. Despite these advances, a comprehensive bibliometric analysis of research trends in glioma chemoradiotherapy resistance over the past two decades is lacking. This study aims to systematically evaluate the research landscape, identify emerging hotspots, and provide guidance for future investigations.MethodsArticles on glioma chemoradiotherapy resistance published between 2003 and 2023 were retrieved from the Web of Science Core Collection, resulting in 4,528 publications. Bibliometric tools, including VOSviewer, CiteSpace, and R packages such as bibliometrix and ggplot2, were used to analyze co-authorship networks, keyword evolution, and citation bursts to identify collaboration patterns, thematic developments, and influential contributions.ResultsPublication output increased significantly between 2013 and 2022, peaking at 650 articles in 2022. Over 1,000 institutions from 88 countries contributed to this research. The United States, Switzerland, and Germany showed the highest citation impact, while China led in publication volume but demonstrated relatively lower citation influence. The research focus has shifted from traditional topics such as the “MGMT gene” to emerging areas including the “tumor microenvironment,” “immune infiltration,” and “nanoparticles.” The androgen receptor was identified as a promising but underexplored therapeutic target.ConclusionsResearch on glioma chemoradiotherapy resistance has seen substantial growth, with increasing emphasis on immune modulation, the tumor microenvironment, and novel therapeutic targets such as the androgen receptor. This study represents the first comprehensive bibliometric analysis of this field, providing a detailed overview of research trends and potential directions for future studies. The findings highlight the need for strengthened international collaboration and multidisciplinary approaches to address the challenges of therapeutic resistance in glioma.
Does pregabalin offer potential as a first-line therapy for generalized anxiety disorder? A meta-analysis of efficacy, safety, and cost-effectiveness
Authors: Cardoner Narcis , Gutiérrez-Rojas Luis , Saiz Pilar , Lahera Guillermo , Álvarez-Mon Miguel Ángel , Alonso Ortega Pino , Pérez-Páramo María 
Published: February 2025

IntroductionGeneralized Anxiety Disorder (GAD) is a mental health condition with a recent increase in prevalence. GAD is often underdiagnosed, leading to negative consequences for individuals, healthcare systems, and society. The economic burden and impaired quality of life associated with GAD underscores the need for effective treatment. Pregabalin has shown promise in reducing anxiety symptoms; however, further research is needed to evaluate its efficacy and compare it with other treatment options. This study aimed to assess the efficacy, safety, and optimal pregabalin dosage for the treatment of GAD.MethodsThis meta-analysis followed PRISMA guidelines. Pregabalin-treated patients comprised the intervention group, whereas the comparator group received benzodiazepines, SSRIs, SNRIs, or placebo. Efficacy and safety were evaluated using various scales and adverse events (AEs). Randomized clinical trials were included in the study. Four major databases were used for this study. Outcome measures included the Hamilton Anxiety Rating Scale (HAM-A), Clinical Global Impression Improvement Scale (CGI-I), discontinuation rates, costs, and quality-adjusted life-years (QALYs). Meta-analyses were conducted using Review Manager 5.4 software, employing odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed based on follow-up and dosage.ResultsFourteen studies involving 4,822 patients were analyzed. Pregabalin demonstrated superior efficacy in reducing HAM-A global scores at 2 weeks (MD −1.23, 95% CI −1.79 to −0.66), 4 weeks (MD −1.12, 95% CI −1.60 to −0.63), 8 weeks (MD −2.50, 95% CI −4.21 to −0.79), 12 weeks (MD 0.99, 95% CI 0.35–1.63), and 6 months to 1 year (MD −3.31, 95% CI −4.30 to −2.31). Pregabalin also showed a higher response rate to HAM-A (OR 1.51, 95% CI 1.31 1.75). CGI-I scores favored pregabalin (MD −0.25, 95% CI −0.38 to −0.12), with a higher response rate (OR 1.33, 95% CI 1.15–1.55). The discontinuation rates were lower with pregabalin (OR 0.80, 95% CI 0.70, 0.91). Adverse events favored pregabalin over SSRIs/SNRIs and benzodiazepines at different doses. Pregabalin was associated with higher cost-effectiveness (MD 0.02, 95% CI 0.01, 0.03).ConclusionPregabalin is an effective and well-tolerated treatment for generalized anxiety disorder, showing superior efficacy and safety compared with first-line medications.Systematic Review RegistrationPROSPERO CRD42024556152.
Anti-TNBC effects of Lappaol F by targeting epithelial-mesenchymal transition via regulation of GSK-3β/YAP/β-catenin and PI3K/AKT pathways
Authors: Meng Qiqi , Li Zhiping , He Xiaofeng , Hu Yuanhao , Wu Guiyun , Huang Jiawen , Luo Zhuohui , Hu Yingjie , Shen Xiaoling 
Published: February 2025

PurposeLappaol F (LAF), a lignan extracted from Fructus Arctii, has a wide spectrum of anti-tumor effects, including inhibition of TNBC cell growth. However, the pharmacological mechanism of LAF targeting epithelial-mesenchymal transition (EMT) to inhibit Triple-negative breast cancer (TNBC) growth remains poorly understood. The present study aimed to reveal the potential mechanism of LAF against TNBC by in vivo and in vitro experiments.MethodsIn situ, transplantation-induced MDA-MB-231 solid tumor model in NCG mice and cultured MDA-MB-231 and Hs-578T cells were used to evaluate the anti-TNBC effect of LAF. Flow cytometry, wound healing, transwell assay, western blot, RT-PCR, and immunofluorescence analysis were carried out to investigate the pharmacological mechanism of LAF against TNBC.ResultsLAF significantly inhibited the growth of MDA-MB-231 tumors, with downregulated tumor level of vimentin and upregulated level of ZO-1. In MDA-MB-231 and Hs-578T cells, LAF markedly suppressed cell proliferation, migration and invasion, and promoted apoptosis. Similarly, LAF increased the expression of ZO-1 and occludin proteins in MDA-MB-231 cells, and inhibited the expression of vimentin, snail and slug proteins in MDA-MB-231 and Hs-578T cells, as well as the expression of N-caderin in Hs-578T cells. Moreover, LAF also inhibited the phosphorylation of GSK-3β, thereby inhibited the downstream nuclear translocation of β-catenin and the expression of YAP. Furthermore, LAF significantly inhibited the expression of PI3K and AKT, and the phosphorylation of downstream mTOR.ConclusionLAF showed anti-TNBC effect both in vitro and in vivo. Reversal of EMT by inhibiting GSK-3β/YAP/β-catenin signaling and PI3K/AKT/mTOR signaling contributes to the effect.
Total flavonoids isolated from Eucommia ulmoides can alleviate bone loss and regulate intestinal microbiota in ovariectomized rats
Authors: Yin Baocang , Yang Mingzhen , Wang Bowen , Zhang Yun , Li Ningli , Li Qin , Li Yingying , Xian Cory J. , Li Tiejun , Zhai Yuankun 
Published: February 2025

Ethnopharmacological relevanceEucommia ulmoides, recognized as a traditional Chinese medicinal herb, can tonify liver and kidney and strengthen bones and muscles. Modern pharmacological research has proved that E. ulmoides could prohibit the occurrence of osteoporosis and arthritis.AimTo investigate the effect and action mechanism of total flavonoids isolated from the leaves of E. ulmoides (TFEL) on bone loss in ovariectomized (OVX) rats, and to study its effect on intestinal flora.Materials and methodsThe 3-month-old female rats were randomly divided into six groups: sham operation group, OVX model group, estradiol group, TFEL low (TFEL-L) (50), mid (-M) (100) and high (-H) (200 mg/kg/d) dose groups. After 13 weeks of treatment, the rats were sacrificed to measure bone turnover markers, related tissue biochemical indices, microstructure parameters, and osteoclastogenesis promotor RANKL and inhibitor OPG expression levels. Additionally, fecal samples were obtained for high-throughput sequencing to analyze the intestinal flora.ResultsOral administration of TFEL for 13 weeks increased the serum level of bone formation marker PINP and decreased the level of bone resorption marker NTX-I. The femoral microstructure parameters of the TFEL-M and TFEL-H groups were significantly improved compared with the OVX group, which were also confirmed by H&amp;E histological staining. High-throughput sequencing indicated that TFEL may regulate the composition of intestinal flora and intestinal microecology.ConclusionTFEL can prevent osteoporosis in OVX rats and has no toxic side effects. Meanwhile, TFEL can increase the diversity and improve the composition of intestinal flora in OVX rats.