bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxymatrine relieves high-fructose/fat-induced obesity via reprogramming the activity of lipid metabolism-related enhancer
Authors: Ren Luping , Liu Xuehua , Huang Xitong , Zhang He , Fei Wenjie , Yu Xian , Hu Zhijuan , Zhen Yunfeng , Chen Shuchun 
Published: August 2023

IntroductionEmerging evidence demonstrates that the high-fructose and high-fat diet (HFHF) induced obesity and fatty liver disease has become one of the most common metabolic disorders worldwide. Therefore, innovative investigations on compounds targeting obesity and fatty liver diseases are urgently needed.MethodsThe high-throughput natural compounds screen was performed to screen the important compounds. A rat HFHF model was constructed, the regulatory function of Oxymatrine in HFHF-induced obesity was further explored.ResultsWe identified Oxymatrine, a natural compound extracted from Sophora flavescens, showed a potential compacity in high-fat diet-induced fatty liver disease. We found that oxymatrine significantly inhibited HFHF-induced obesity using a rat HFHF model. Additionally, we found that oxymatrine altered the enhancer landscape of subcutaneous adipose tissues by ChIP-seq analysis using antibodies against the H3K27ac histone modification. Motif enrichment analysis showed the Smad motif was significantly enriched in enhancers altered post-oxymatrine treatment. Further chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) analysis and luciferase reporter assays showed oxymatrine alters the binding of Smad3 on the enhancer regions of B-cell lymphoma 2 (Bcl2) and the enhancer activity of Bcl2.DiscussionTogether, our study highlighted oxymatrine could suppress high-fructose and high-fat diet-induced obesity by inhibiting the suppressor of mothers against decapentaplegic 3 (Smad3) binding on obesity-related enhancers.
Leveraging senescence-oxidative stress co-relation to predict prognosis and drug sensitivity in breast invasive carcinoma
Authors: Ye Yinghui , Luo Yulou , Guo Tong , Zhang Chenguang , Sun Yutian , Xu Anping , Ji Ling , Ou Jianghua , Wu Shang Ying 
Published: August 2023

IntroductionFemale breast cancer has risen to be the most common malignancy worldwide, causing a huge disease burden for both patients and society. Both senescence and oxidative stress attach importance to cancer development and progression. However, the prognostic roles of senescence and oxidative stress remain obscure in breast cancer. In this present study, we attempted to establish a predictive model based on senescence-oxidative stress co-relation genes (SOSCRGs) and evaluate its clinical utility in multiple dimensions.MethodsSOSCRGs were identified via correlation analysis. Transcriptome data and clinical information of patients with breast invasive carcinoma (BRCA) were accessed from The Cancer Genome Atlas (TCGA) and GSE96058. SVM algorithm was employed to process subtype classification of patients with BRCA based on SOSCRGs. LASSO regression analysis was utilized to establish the predictive model based on SOSCRGs. Analyses of the predictive model with regards to efficacy evaluation, subgroup analysis, clinical association, immune infiltration, functional strength, mutation feature, and drug sensitivity were organized. Single-cell analysis was applied to decipher the expression pattern of key SOSCRGs in the tumor microenvironment. Additionally, qPCR was conducted to check the expression levels of key SOSCRGs in five different breast cancer cell lines.ResultsA total of 246 SOSCRGs were identified. Two breast cancer subtypes were determined based on SOSCRGs and subtype 1 showed an active immune landscape. A SOSCRGs-based predictive model was subsequently developed and the risk score was clarified as independent prognostic predictors in breast cancer. A novel nomogram was constructed and exhibited favorable predictive capability. We further ascertained that the infiltration levels of immune cells and expressions of immune checkpoints were significantly influenced by the risk score. The two risk groups were characterized by distinct functional strengths. Sugar metabolism and glycolysis were significantly upregulated in the high risk group. The low risk group was deciphered to harbor PIK3CA mutation-driven tumorigenesis, while TP53 mutation was dominant in the high risk group. The analysis further revealed a significantly positive correlation between risk score and TMB. Patients in the low risk group may also sensitively respond to several drug agents. Single-cell analysis dissected that ERRFI1, ETS1, NDRG1, and ZMAT3 were expressed in the tumor microenvironment. Moreover, the expression levels of the seven SOSCRGs in five different breast cancer cell lines were quantified and compared by qPCR respectively.ConclusionMultidimensional evaluations verified the clinical utility of the SOSCRGs-based predictive model to predict prognosis, aid clinical decision, and risk stratification for patients with breast cancer.
Immune-related gene IL17RA as a diagnostic marker in osteoporosis
Authors: Deng Ya-Jun , Li Zhi , Wang Bo , Li Jie , Ma Jun , Xue Xiong , Tian Xin , Liu Quan-Cheng , Zhang Ying , Yuan Bin 
Published: August 2023

Objectives: Bone immune disorders are major contributors to osteoporosis development. This study aims to identify potential diagnostic markers and molecular targets for osteoporosis treatment from an immunological perspective.Method: We downloaded dataset GSE56116 from the Gene Expression Omnibus database, and identified differentially expressed genes (DEGs) between normal and osteoporosis groups. Subsequently, differentially expressed immune-related genes (DEIRGs) were identified, and a functional enrichment analysis was performed. A protein-protein interaction network was also constructed based on data from STRING database to identify hub genes. Following external validation using an additional dataset (GSE35959), effective biomarkers were confirmed using RT-qPCR and immunohistochemical (IHC) staining. ROC curves were constructed to validate the diagnostic values of the identified biomarkers. Finally, a ceRNA and a transcription factor network was constructed, and a Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed to explore the biological functions of these diagnostic markers.Results: In total, 307 and 31 DEGs and DEIRGs were identified, respectively. The enrichment analysis revealed that the DEIRGs are mainly associated with Gene Ontology terms of positive regulation of MAPK cascade, granulocyte chemotaxis, and cytokine receptor. protein–protein interaction network analysis revealed 10 hub genes: FGF8, KL, CCL3, FGF4, IL9, FGF9, BMP7, IL17RA, IL12RB2, CD40LG. The expression level of IL17RA was also found to be significantly high. RT-qPCR and immunohistochemical results showed that the expression of IL17RA was significantly higher in osteoporosis patients compared to the normal group, as evidenced by the area under the curve Area Under Curve of 0.802. Then, we constructed NEAT1-hsa-miR-128-3p-IL17RA, and SNHG1-hsa-miR-128-3p-IL17RA ceRNA networks in addition to ERF-IL17RA, IRF8-IL17RA, POLR2A-IL17RA and ERG-IL17RA transcriptional networks. Finally, functional enrichment analysis revealed that IL17RA was involved in the development and progression of osteoporosis by regulating local immune and inflammatory processes in bone tissue.Conclusion: This study identifies the immune-related gene IL17RA as a diagnostic marker of osteoporosis from an immunological perspective, and provides insight into its biological function.
The efficacy of botulinum toxin type A treatment and surgery for acute acquired comitant esotropia
Authors: Li Yipao , Tong Luyao , Chen Yuanyuan , Zhang BinJun , Wan Minghui , Yin Xiangping , Zhang Fang 
Published: August 2023

AimTo compare the long-term efficiency of botulinum toxin type A (BTXA) injection and surgery on acute acquired comitant esotropia (AACE).MethodsThis retrospective study enrolled patients with AACE from January 2020 to August 2022. The horizontal angle of deviation pre- and post-treatment was measured. Deviations in BTXA and surgical treatment were compared. The BTXA group was divided into adequate treatment (AT) and inadequate treatment (inAT) subgroup based on the deviation of no more than 4 prism diopters (at near and distance) or temporary exotropia at the 2 week follow-up. The two subgroups were compared to determine the long-term efficacy of BTXA treatment.ResultsNinety-two patients with AACE were included. Follow-up was 6 months. The deviations of the surgery and BTXA group were significantly smaller at the 6 month follow-up than at pre-treatment (p &lt; 0.001). The deviation before treatment in the surgery group was larger than in the BTXA groups (p &lt; 0.001) but smaller at the 6 month follow-up (p &lt; 0.001). The deviation was similar in the AT-BTXA and inAT-BTXA subgroups before treatment (p = 0.322 for distance and p = 0.051 for near) but smaller in the AT-BTXA subgroup at 6 month follow-up (p &lt; 0.001 for near and distance).ConclusionSurgery and BTXA successfully treat AACE. Surgery has a more precise and lasting therapeutic effect than BTXA. AACE patients adequately treated with BTXA and with deviations of no more than 4 prism diopters at 2 weeks follow-up had better outcomes.
Identification of disulfidptosis-related genes and subgroups in Alzheimer’s disease
Authors: Ma Shijia , Wang Dan , Xie Daojun 
Published: August 2023

BackgroundAlzheimer’s disease (AD), a common neurological disorder, has no effective treatment due to its complex pathogenesis. Disulfidptosis, a newly discovered type of cell death, seems to be closely related to the occurrence of various diseases. In this study, through bioinformatics analysis, the expression and function of disulfidptosis-related genes (DRGs) in Alzheimer’s disease were explored.MethodsDifferential analysis was performed on the gene expression matrix of AD, and the intersection of differentially expressed genes and disulfidptosis-related genes in AD was obtained. Hub genes were further screened using multiple machine learning methods, and a predictive model was constructed. Finally, 97 AD samples were divided into two subgroups based on hub genes.ResultsIn this study, a total of 22 overlapping genes were identified, and 7 hub genes were further obtained through machine learning, including MYH9, IQGAP1, ACTN4, DSTN, ACTB, MYL6, and GYS1. Furthermore, the diagnostic capability was validated using external datasets and clinical samples. Based on these genes, a predictive model was constructed, with a large area under the curve (AUC = 0.8847), and the AUCs of the two external validation datasets were also higher than 0.7, indicating the high accuracy of the predictive model. Using unsupervised clustering based on hub genes, 97 AD samples were divided into Cluster1 (n = 24) and Cluster2 (n = 73), with most hub genes expressed at higher levels in Cluster2. Immune infiltration analysis revealed that Cluster2 had a higher level of immune infiltration and immune scores.ConclusionA close association between disulfidptosis and Alzheimer’s disease was discovered in this study, and a predictive model was established to assess the risk of disulfidptosis subtype in AD patients. This study provides new perspectives for exploring biomarkers and potential therapeutic targets for Alzheimer’s disease.
Findings of a videofluoroscopic swallowing study in patients with dysphagia
Authors: Cui Qingjia , Wei Bing , He Yuan , Zhang Qian , Jia Weiwei , Wang Haiying , Xi Jianing , Dai Xin 
Published: August 2023

ObjectiveSwallowing examination is crucial in patients with dysphagia. We aimed to compare qualitative and quantitative videofluoroscopic swallowing study (VFSS) results to provide reference for standardizing quantitative parameters.Materials and methodsIn total, 117 patients with dysphagia were included, 38 with Parkinson’s disease and 39 and 40 in convalescence following cerebral hemorrhage and infarction. VFSS was both qualitatively and quantitatively analyzed.ResultsA significant difference of Oral transit time was found between the oral motor function grades (p &lt; 0.001), also was swallowing reaction times found between swallowing reaction duration grades (p &lt; 0.001), and soft palate lift duration between the soft palate lift grades (p &lt; 0.001). Superior hyoid bone movement (p &lt; 0.001), anterior hyoid bone movement (p &lt; 0.001), hyoid pause time (p &lt; 0.001), and hyoid movement duration (p = 0.032) had significant differences between the hyoid laryngeal complex movement grades, as did the pharyngeal cavity transit time among the cricopharyngeal muscle opening duration grades (p &lt; 0.001). The laryngeal vestibule closure duration differed among the glottic closure grades (p &lt; 0.001). No statistically significant difference in upper esophageal sphincter opening diameter (p = 0.682) or duration (p = 0.682) among the cyclopharyngeal muscle opening duration grades. The pharyngeal area at rest did not significantly differ among the different vallecular residue (p = 0.202) and pyriform sinus residue (p = 0.116) grades.ConclusionSeveral quantitative parameters can reflect the swallowing assessment process well. Further optimization of quantitative parameters is recommended.
Impact of ongoing intravenous thrombolysis until completion of endovascular treatment in large vessel occlusion stroke patients
Authors: Wischmann Johannes , Pradhan Cauchy , Zimmermann Hanna , Keidel Linus , Tiedt Steffen , Dimitriadis Konstantinos , Liebig Thomas , Höglinger Günter , Kellert Lars 
Published: August 2023

BackgroundRecent studies have implied that ongoing intravenous thrombolysis (IVT) during endovascular treatment (ET) improves functional outcomes in patients who have undergone stroke caused by a large vessel occlusion (LVO). In this study, we investigated the effect of ongoing IVT until completion of ET on procedure duration, first-pass thrombectomy rate, and periprocedural complications.MethodsWe analyzed patients from the German Stroke Registry-Endovascular Treatment dataset, collected between June 2015 and December 2021. Primary outcomes were modified Rankin Scale (mRS) score after 3 months and achievement of a Thrombolysis In Cerebral Infarction (TICI) score of 2b-3. Secondary parameters included ET duration, first-pass thrombectomy, and periprocedural complications.ResultsOf the 13,082 patients in the dataset, 1,639 met the study inclusion criteria. A total of n = 317 patients (19.3%) underwent ongoing IVT until completion of ET, while IVT was completed prior to ET in 1,322 patients (80.7%). Ongoing IVT was associated with higher rates of achievement of an mRS score of 0–2 (or a back-to-baseline) after 3 months [odds ratio (OR) 1.53; 95% confidence interval (CI) 1.08–2.17]. Furthermore, ongoing IVT was predictive of achievement of a TICI score of 2b-3 (OR 1.37; 95% CI 1.03–1.83) and of first-pass thrombectomy (OR 2.07; 95% CI 1.51–2.84), while reducing the rate of peri-interventional complications (OR 0.64; 95% CI 0.44–0.94) and reducing ET duration by 24 min [β = −24.35; 95% CI −32.92–(−15.79)].ConclusionOur findings suggest that ongoing IVT until ET completion has a favorable impact on both clinical and angiographic outcomes, as well as on periprocedural conditions, regardless of the overall time intervals involved. Therefore, rapid ET after IVT should be sought in order to take advantage of the additive effect of ongoing IVT during ET. Future studies should consider IVT timing in the context of ET as a potential confounder and treatment target.
Assessment of COVID-19-related olfactory dysfunction and its association with psychological, neuropsychiatric, and cognitive symptoms
Authors: Jegatheeswaran Lavandan , Gokani Shyam Ajay , Luke Louis , Klyvyte Gabija , Espehana Andreas , Garden Elizabeth Mairenn , Tarantino Alessia , Al Omari Basil , Philpott Carl Martin 
Published: August 2023

Purpose of reviewTo provide a detailed overview of the assessment of COVID-19-related olfactory dysfunction and its association with psychological, neuropsychiatric, and cognitive symptoms.Recent findingsCOVID-19-related olfactory dysfunction can have a detrimental impact to the quality of life of patients. Prior to the COVID-19 pandemic, olfactory and taste disorders were a common but under-rated, under-researched and under-treated sensory loss. The pandemic has exacerbated the current unmet need for accessing good healthcare for patients living with olfactory disorders and other symptoms secondary to COVID-19. This review thus explores the associations that COVID-19 has with psychological, neuropsychiatric, and cognitive symptoms, and provide a framework and rationale for the assessment of patients presenting with COVID-19 olfactory dysfunction.SummaryAcute COVID-19 infection and long COVID is not solely a disease of the respiratory and vascular systems. These two conditions have strong associations with psychological, neuropsychiatric, and cognitive symptoms. A systematic approach with history taking and examination particularly with nasal endoscopy can determine the impact that this has on the patient. Specific olfactory disorder questionnaires can demonstrate the impact on quality of life, while psychophysical testing can objectively assess and monitor olfaction over time. The role of cross-sectional imaging is not yet described for COVID-19-related olfactory dysfunction. Management options are limited to conservative adjunctive measures, with some medical therapies described.
Association between added sugars and kidney stones in U.S. adults: data from National Health and Nutrition Examination Survey 2007–2018
Authors: Yin Shan , Yang Zhenzhen , Zhu Pingyu , Du Zhongbo , Yu Xiaodong , Tang Tielong , Borné Yan 
Published: August 2023

PurposeAdded sugar is associated with a variety of adverse health outcomes, but its association with kidney stones is unclear. This study was to determine whether added sugar is associated with kidney stones.Materials and methodsThis nationally representative study used National Health and Nutrition Examination Survey (NHANES) datasets from 2007 to 2018 for analysis. People aged ≥20 years who reported a history of kidney stones and provided dietary recall data on added sugars were included. Weighted proportions, multivariable logistic regression analysis and stratified logistic regression were used to evaluate the associations between added sugars and kidney stones by adjusting potential confounders.ResultsTotally 28,303 adults were included, with weighted mean age [95% confidence interval (CI)] of 48.03 (47.56, 48.51) years, 47.74% (47.09, 48.40%) males and 52.26% (51.60, 52.91%) females. The overall mean (95% CI) energy intake from added sugars was 272.10 (266.59, 277.60) kilocalories. In the fully-adjusted multivariable model, the percentage of energy intake from added sugars was positively correlated with kidney stones. Compared to the first quartile of added sugar energy intake percentage, the population in the fourth quartile had a higher prevalence of kidney stones (OR = 1.39; 95% CI 1.17 to 1.65). Compared with the less than 5% calories from added sugar population, the more than or equal to 25% calories from added sugar had a higher kidney stone prevalence (OR = 1.88; 95% CI 1.52 to 2.32).ConclusionA higher percentage of energy intake from added sugars is significantly associated with a higher prevalence of kidney stones. This study provides cross-sectional evidence for the relationship between added sugars and health outcomes.
A nomogram for predicting the risk of male breast cancer for overall survival
Authors: Wen Yahui , Bai Junjie , Zheng Caihong , Liu Jiameng , Lin Shunguo , Han Hui , Xu Chunsen 
Published: August 2023

BackgroundMale breast cancer (MBC) is a rare disease, accounting for &lt;1% of all male carcinomas. Lack of prospective data, the current therapy for MBC is based on retrospective analysis or information that is extrapolated from studies of female patients. We constructed a nomogram model for predicting the overall survival (OS) of MBC patients and verify its feasibility using data from China.MethodsConstructed a predictive model using 1224 MBC patients from the Surveillance, Epidemiology and End Results (SEER) registry between 2010 and 2015. The performance of the model was externally validated between 2002 to 2021 using 44 MBC patients from the Fujian Medical University Union Hospital. The independent prognostic factors were selected by univariate and multivariate Cox regression analyses. The nomogram was constructed to predict individual survival outcomes for MBC patients. The discriminative power, calibration, and clinical effectiveness of the nomogram were evaluated by the receiver operating characteristic (ROC) curve, and the decision curve analysis (DCA).ResultsA total of 1224 male breast cancer patients were in the training cohort and 44 in the validation cohort. T status (p&lt;0.001), age at diagnosis (p&lt;0.001), histologic grade (p=0.008), M status (p&lt;0.001), ER status (p=0.001), Her2 status (p=0.019), chemotherapy (p=0.015) were independently associated with OS. The diagnostic performance of this model was evaluated and validated using ROC curves on the training and validation datasets. In the training cohort, the nomogram-predicted AUC value was 0.786 for 3-year OS and 0.767 for 5-year OS. In the validation cohort, the nomogram-predicted AUC value was 0.893 for 3-year OS and 0.895 for 5-year OS. Decision curve analysis demonstrated that the nomogram was more benefit than the AJCC stage.ConclusionsWe developed a nomogram that predicts 3-year and 5-year survival in MBC patients. Validation using bootstrap sampling revealed optimal discrimination and calibration, suggesting that the nomogram may have clinical utility. The results remain reproducible in the validation cohort which included Chinese data. The model was superior to the AJCC stage system as shown in the decision curve analysis (DCA).
Taxonomic and functional profiling of fecal metagenomes for the early detection of colorectal cancer
Authors: Wu Xudong , Tang Zhimin , Zhao Rongsong , Wang Yusi , Wang Xianshu , Liu Side , Zou Hongzhi 
Published: August 2023

ObjectivesThis study aimed to identify colorectal cancer (CRC)-associated phylogenetic and functional bacterial features by a large-scale metagenomic sequencing and develop a binomial classifier to accurately distinguish between CRC patients and healthy individuals.MethodsWe conducted shotgun metagenomic analyses of fecal samples from a ZhongShanMed discovery cohort of 121 CRC and 52 controls and SouthernMed validation cohort of 67 CRC and 44 controls. Taxonomic profiling and quantification were performed by direct sequence alignment against genome taxonomy database (GTDB). High-quality reads were also aligned to IGC datasets to obtain functional profiles defined by Kyoto Encyclopedia of Genes and Genomes (KEGG). A least absolute shrinkage and selection operator (LASSO) classifier was constructed to quantify risk scores of probability of disease and to discriminate CRC from normal for discovery, validation, Fudan, GloriousMed, and HongKong cohorts.ResultsA diverse spectrum of bacterial and fungi species were found to be either enriched (368) or reduced (113) in CRC patients (q&lt;0.05). Similarly, metabolic functions associated with biosynthesis and metabolism of amino acids and fatty acids were significantly altered (q&lt;0.05). The LASSO regression analysis of significant changes in the abundance of microbial species in CRC achieved areas under the receiver operating characteristic curve (AUROCs) of 0.94 and 0.91 in the ZhongShanMed and SouthernMed cohorts, respectively. A further analysis of Fudan, GloriousMed, and HK cohorts using the same classification model also demonstrated AUROC of 0.80, 0.78, and 0.91, respectively. Moreover, major CRC-associated bacterial biomarkers identified in this study were found to be coherently enriched or depleted across 10 metagenomic sequencing studies of gut microbiota.ConclusionA coherent signature of CRC-associated bacterial biomarkers modeled on LASSO binomial classifier maybe used accurately for early detection of CRC.