bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and Validation of the N6-Methyladenosine RNA Methylation Regulator YTHDF1 as a Novel Prognostic Marker and Potential Target for Hepatocellular Carcinoma
Authors: Bian Saiyan , Ni Wenkai , Zhu Mengqi , Song Qianqian , Zhang Jianping , Ni Runzhou , Zheng Wenjie 
Published: December 2020

Purpose: N6-methyladenosine (m6A) RNA methylation has been implicated in various malignancies. This study aimed to identify the m6A methylation regulator-based prognostic signature for hepatocellular carcinoma (HCC) as well as provide candidate targets for HCC treatment.Methods: The least absolute shrinkage and selection operator (LASSO) analyses were performed to identify a risk signature in The Cancer Genome Atlas (TCGA) datasets. The risk signature was further validated in International Cancer Genome Consortium (ICGC) and Pan-Cancer Analysis of Whole Genomes (PCAWG) datasets. Following transfection of short hairpin RNA (shRNA) targeting YTHDF1, the biological activities of HCC cells were evaluated by Cell Counting Kit-8 (CCK-8), wound-healing, Transwell, flow cytometry, and xenograft tumor assays, respectively. The potential mechanisms mediated by YTHDF1 were predicted by overrepresentation enrichment analysis (ORA)/gene set enrichment analysis (GSEA) and validated by Western blotting.Results: Overexpression of m6A RNA methylation regulators was correlated with malignant clinicopathological characteristics of HCC patients. The Cox regression and LASSO analyses identified a risk signature with five m6A methylation regulators (KIAA1429, ZC3H13, YTHDF1, YTHDF2, and METTL3). In accordance with HCC cases in TCGA, the prognostic value of risk signature was also determined in ICGC and PCAWG datasets. Following analyzing the expression and clinical implications in TCGA and Gene Expression Omnibus (GEO), YTHDF1 was chosen for further experimental validation. Knockdown of YTHDF1 significantly inhibited the proliferation, migration, and invasion of HCC cells, as well as enhanced the apoptosis in vitro. Moreover, silencing YTHDF1 repressed the growth of xenograft tumors in vivo. Mechanism investigation indicated that YTHDF1 might promote the aggressive phenotypes by facilitating epithelial–mesenchymal transition (EMT) and activating AKT/glycogen synthase kinase (GSK)-3β/β-catenin signaling.Conclusion: The current study identified a robust risk signature consisting of m6A RNA methylation regulators for HCC prognosis. In addition, YTHDF1 was a potential molecular target for HCC treatment.
Prevalence and Risk Factors for Malnutrition in Patients With Parkinson's Disease
Authors: Yang Tianting , Zhan Zhen , Zhang Liang , Zhu Jun , Liu Yi , Zhang Lili , Ge Jianchao , Zhao Ying , Zhang Li , Dong Jingde 
Published: December 2020

Objectives: This study aimed to investigate the relationship between nutritional status and Parkinson's disease (PD) features.Methods: The cohort was composed of 556 Parkinson's patients who were admitted to the hospital. Patients were categorized as normal nutrition or at risk of malnutrition/already malnourished. Questionnaires, physical examinations, and biochemical tests were conducted. The relationship between nutrition status and PD was analyzed using t-tests, χ2-tests, and logistic regression models.Results: The prevalence of malnutrition [defined as a Mini Nutritional Assessment (MNA) score &lt;17] was 39.2%, and 30.3% of patients were at risk of malnutrition (17 ≤ MNA score ≤ 23.5). There was no difference in gender and age between the different nutrition groups (P &lt; 0.05). Patients at risk of malnutrition and those who were malnourished had a longer course of disease, more severe motor symptoms, a higher stage of PD according to the Hoehn and Yahr (H-Y) classification, a lower body mass index (BMI) index, a lower cognitive score, higher levels of depression and anxiety, and more serious non-motor symptoms (P &lt; 0.05) than patients with normal nutrition. There were differences in adenosine deaminase, albumin, phosphorus, chlorine, total protein, and uric acid between the two groups (P &lt; 0.05). High Unified PD Rating Scale (UPDRS-III) scores, high H-Y stages, and dyskinesia were risk factors for malnutrition in PD patients, while high levels of total protein, uric acid, and chlorine were protective factors that led to good nutrition (P &lt; 0.05).Conclusions: Our results showed that dyskinesia, disease severity, total protein levels, uric acid levels, and chlorine levels were associated with nutritional status among Chinese PD patients. The findings of this study indicate the significance of the early detection and prevention of malnutrition to improve the quality of life of PD patients.
Qualitative and Quantitative Wall Enhancement Analyses in Unruptured Aneurysms Are Associated With an Increased Risk of Aneurysm Instability
Authors: Zhang Yi , Fu Qichang , Wang Yuting , Cheng Jingliang , Ren Cuiping , Guan Sheng , Zhu Chengcheng 
Published: December 2020

ObjectiveIntracranial aneurysm wall enhancement (AWE) is independently associated with unstable aneurysms. However, a quantitative analysis of wall enhancement is lacking. This study aims to investigate the relationship between qualitative and quantitative wall enhancement indices (WEIs), traditional risk factors for aneurysms, and clinical ELAPSS/PHASES scores in a large cohort of intracranial saccular aneurysms.Materials and MethodsIn this cross-sectional study, a total of 174 patients (mean age 60.4 ± 9.5 years; 53% women) with 248 asymptomatic unruptured intracranial aneurysms underwent pre- and post-contrast black-blood magnetic resonance imaging (MRI). The extent of AWE was defined as non-AWE (pattern 0), focal AWE (pattern 1), or circumferential AWE (pattern 2). WEI was calculated using wall signal intensities on pre- and post-contrast images. Predicted 3- and 5-year growth risk and 5-year rupture risk were obtained from ELAPSS and PHASES scores, respectively. Uni- and multivariate analyses were conducted to explore the relationship between AWE characteristics, risk-related factors, and aneurysm instability.ResultsAneurysm size [odds ratio (OR), 1.3; 95% confidence interval (CI), 1.2–1.4; P &lt; 0.001], non-internal carotid artery/middle cerebral artery location (OR, 1.9; 95% CI, 1.0–3.6; P = 0.045), and irregular shape (OR, 2.4; 95% CI, 1.2–4.5; P = 0.009) were independently associated with AWE. For aneurysms with AWE, the estimated 3- and 5-year growth risk (25.3 ± 13.0% and 38.0 ± 17.4%) and the 5-year rupture risk (3.9 ± 5.2%) were 1.9–3.3 times higher than those for aneurysms without AWE (12.8 ± 9.1%, 20.3 ± 13.0%, and 1.2 ± 1.6%, respectively; all P &lt; 0.001). Larger areas and higher WEIs of enhancement positively correlated with aneurysm size (r = 0.43 and 0.38, respectively), 3- and 5-year growth risk, and 5-year rupture risk (r = 0.49 and 0.40, r = 0.49 and 0.40, r = 0.36 and 0.24, respectively; all P &lt; 0.001). In sum, a larger aneurysm size, non-internal carotid artery/middle cerebral artery location, and irregular shape were independently associated with AWE. Larger areas and higher WEIs were associated with an increased risk of aneurysm growth and rupture. These findings suggest that quantitative AWE metrics should be considered in future large-scale longitudinal studies to evaluate their value in aneurysm risk management.
Stereotactic Body Radiation Therapy: A Versatile, Well-Tolerated, and Effective Treatment Option for Extracranial Metastases From Primary Ovarian and Uterine Cancer
Authors: Aghdam Nima , Repka Michael C. , McGunigal Mary , Pepin Abby , Paydar Ima , Rudra Sonali , Paudel Nitika , Pernia Marin Monica , Suy Simeng , Collins Sean P. , Barnes Willard , Collins Brian T. 
Published: December 2020

PurposeSingle extracranial metastases from ovarian and uterine malignancies have historically been treated with surgery or conventional radiation. We report mature local control (LC), overall survival (OS), progression free survival (PFS), and toxicity for patients who completed 5-fraction stereotactic body radiation therapy (SBRT).MethodsPatients with biopsy-proven, single extracranial metastases from primary ovarian and uterine malignancies treated with 5-fraction SBRT were included. Patients were stratified based on tumor volume (small &lt; 50 cc or large ≥ 50 cc) and dose (low dose &lt; 35 Gy or high ≥ 35 Gy). Kaplan–Meier method was used to estimate LC, OS, and PFS.ResultsBetween July 2007 and July 2012, 20 patients underwent SBRT to a single extracranial metastasis. Primary site was divided evenly between ovarian and uterine (n = 10 each). Metastases involved the liver (30%), abdominal lymph nodes (25%), lung (20%), pelvic lymph nodes (10%), spine (10%), and extremity (5%). The median gross tumor volume (GTV) was 42.5 cc (range, 5–273 cc) and the median dose to the GTV was 35 Gy (range, 30–50 Gy). At a median follow-up of 56 months, the 5-year LC and OS estimates were 73 and 46%. When stratified by tumor volume, the 5-year LC and OS for small tumors were significantly better at 100% (p &lt; 0.01) and 65% (p &lt; 0.02). When stratified by dose, the 5-year LC was 87.5% with high dose and 53.6% with low dose (p = 0.035). The 5-year PFS for the entire cohort was 20%. Four patients with small metastases who had complete response remained disease free at study completion and were considered cured (median PFS &gt; 10 years). Treatment was generally well tolerated, and only one patient experienced a late grade III musculoskeletal SBRT related toxicity.ConclusionsSBRT is a versatile, well-tolerated, and effective treatment option for single extracranial metastases from ovarian and uterine primary tumors. 35 Gy in five fractions appears to be a practical minimum effective dose. Four patients with small metastases were disease free at the study completion and considered cured. However, patients with larger metastases (≥50 cc) may require higher SBRT dosing or alternative treatments.
Systemic Inflammation Response Index Is a Predictor of Poor Survival in Locally Advanced Nasopharyngeal Carcinoma: A Propensity Score Matching Study
Authors: Feng Yuhua , Zhang Na , Wang Sisi , Zou Wen , He Yan , Ma Jin-an , Liu Ping , Liu Xianling , Hu Chunhong , Hou Tao 
Published: December 2020

IntroductionNasopharyngeal carcinoma (NPC) is a common malignancy in China and known prognostic factors are limited. In this study, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), and systemic inflammation response index (SIRI) were evaluated as prognostic factors in locally advanced NPC patients.Materials and MethodsNPC patients who received curative radiation or chemoradiation between January 2012 and December 2015 at the Second Xiangya Hospital were retrospectively reviewed, and a total of 516 patients were shortlisted. After propensity score matching (PSM), 417 patients were eventually enrolled. Laboratory and clinical data were collected from the patients’ records. Receiver operating characteristic curve analysis was used to determine the optimal cut-off value. Survival curves were analyzed using the Kaplan-Meier method. The Cox proportional hazard model was used to identify prognostic variables.ResultsAfter PSM, all basic characteristics between patients in the high SIRI group and low SIRI group were balanced except for sex (p=0.001) and clinical stage (p=0.036). Univariate analysis showed that NLR (p=0.001), PLR (p=0.008), SII (p=0.001), and SIRI(p&lt;0.001) were prognostic factors for progression-free survival (PFS) and overall survival (OS). However, further multivariate Cox regression analysis showed that only SIRI was an independent predictor of PFS and OS (hazard ratio (HR):2.83; 95% confidence interval (CI): 1.561-5.131;p=0.001, HR: 5.19; 95% CI: 2.588-10.406;p&lt;0.001), respectively.ConclusionOur findings indicate that SIRI might be a promising predictive indicator of locally advanced NPC patients.
Integrative Analysis of Multi-Omics Identified the Prognostic Biomarkers in Acute Myelogenous Leukemia
Authors: Zheng Jiafeng , Zhang Tongqiang , Guo Wei , Zhou Caili , Cui Xiaojian , Gao Long , Cai Chunquan , Xu Yongsheng 
Published: December 2020

BackgroundAcute myelogenous leukemia (AML) is a common pediatric malignancy in children younger than 15 years old. Although the overall survival (OS) has been improved in recent years, the mechanisms of AML remain largely unknown. Hence, the purpose of this study is to explore the differentially methylated genes and to investigate the underlying mechanism in AML initiation and progression based on the bioinformatic analysis.MethodsMethylation array data and gene expression data were obtained from TARGET Data Matrix. The consensus clustering analysis was performed using ConsensusClusterPlus R package. The global DNA methylation was analyzed using methylationArrayAnalysis R package and differentially methylated genes (DMGs), and differentially expressed genes (DEGs) were identified using Limma R package. Besides, the biological function was analyzed using clusterProfiler R package. The correlation between DMGs and DEGs was determined using psych R package. Moreover, the correlation between DMGs and AML was assessed using varElect online tool. And the overall survival and progression-free survival were analyzed using survival R package.ResultsAll AML samples in this study were divided into three clusters at k = 3. Based on consensus clustering, we identified 1,146 CpGs, including 40 hypermethylated and 1,106 hypomethylated CpGs in AML. Besides, a total 529 DEGs were identified, including 270 upregulated and 259 downregulated DEGs in AML. The function analysis showed that DEGs significantly enriched in AML related biological process. Moreover, the correlation between DMGs and DEGs indicated that seven DMGs directly interacted with AML. CD34, HOXA7, and CD96 showed the strongest correlation with AML. Further, we explored three CpG sites cg03583857, cg26511321, cg04039397 of CD34, HOXA7, and CD96 which acted as the clinical prognostic biomarkers.ConclusionOur study identified three novel methylated genes in AML and also explored the mechanism of methylated genes in AML. Our finding may provide novel potential prognostic markers for AML.
Comprehensive Molecular Characterizations of Chinese Patients With Different Subtypes of Lung Squamous Cell Carcinoma
Authors: Qian Jie , Chen Rongrong , Zhao Ruiying , Han Yuchen , Yu Yongfeng 
Published: December 2020

BackgroundThis study aims to profile integrative genomic spectra of Chinese patients with different subtypes of lung squamous cell carcinoma (LUSC) and explore potential molecular prognosis factors.MethodsWe retrospectively identified 204 surgically resected LUSC patients in Shanghai Chest Hospital who underwent capture-based targeted next-generation sequencing (NGS) with a panel of 68 lung cancer‐related genes from September 2017 to January 2019. NGS was used to profile comprehensive molecular characterizations.ResultsOf 204 cases, 114 (55.9%) were keratinizing squamous cell carcinoma (KSCC), 77 (37.7%) were non-keratinizing squamous cell carcinoma (NKSCC), 13 (6.4%) were basaloid squamous cell carcinoma (BSCC), respectively. All subtypes presented similarly high proportions of mutations, including TP53, CDKN2A, and NOTCH1. A comparable prevalence of FGFR1 amplifications was identified between KSCC and NKSCC (11.4 versus 26.9%, p = 0.007). Compared with NKSCC, IGF1R amplifications were more frequent in BSCC (0 versus 15.4%, p = 0.019). We found cases with TP53 alterations had less EGFR alterations in KSCC (P = 0.013, OR = 0.158). Compared with TCGA cohorts, our Chinese cohorts exhibited statistic differences in both somatic mutations and signaling pathways. We found that STK 11 alterations and TOP2A alterations were significantly associated with higher risk of recurrence in patients with LUSC.ConclusionsSignificant differences exist among three subtypes of LUSC in molecular characterizations.
A Novel, Portable MESH Nebulizer—An Alternative to Metered Dose Inhaler: Efficacy and Usability in Preschool Wheezers
Authors: Ullmann Nicola , Di Marco Antonio , Columbu Fabiana , Negro Valentina , Chiarini Testa Maria Beatrice , Panetta Valentina , Tripodi Salvatore , Potapova Ekaterina , Allegorico Annalisa , Matricardi Paolo Maria , Cutrera Renato 
Published: December 2020

Introduction and Objectives: Wheezing episodes are the first causes of doctor's consultation in preschool age. Treatment is usually administered with a metered dose inhaler (MDI) spacer. At variance, many parents and doctors prefer to use a compressor nebulizer, which cannot be easily carried. The study is aimed at testing whether a pocket mesh nebulizer has similar efficacy and acceptability than a standard MDI device.Materials and Methods: The IPAC study was a randomized, controlled, non-inferiority trial (number: 1616/2018, Ospedale Pediatrico Bambino Gesu'—IRCCS). The study had two arms: cases, using MicroAIR U100, and controls, using MDI+spacer device. Both devices were adopted for long-term treatment and for exacerbations. Follow-up was organized with clinical visits and a daily e-diary connected to an application for mobile phone.Results: One hundred patients were enrolled. The frequency of asthmatic symptoms showed a non-inferiority for MicroAIR U100 group vs. MDI. Accordingly, no significant difference was found in the average % of days with cough, wheezing, breathlessness after exercise, days lost at school, and not-programmed visits. Considering only patients with &gt;1 day with symptoms, no significant sdifferences were found in the number of exacerbations nor in the cumulative days with symptoms. The acceptance and usability of both devices have been favorable. However, the MDI+AeroChamber® device showed better acceptability.Conclusions: Our study shows that MicroAIR U-100, a mesh nebulizer, has similar clinical efficacy but lower acceptance and usability than an MDI plus Aerochamber® in delivering therapy in preschool wheezers. Therefore, MicroAIR U-100 might be a valuable second choice, when the delivery of medication with an MDI plus Aerochamber® is not accepted, or wrongly used by the parents.
Socio-Demographic Factors Affect the Prevalence of Hematuria and Proteinuria Among School Children in Hualien, Taiwan: A Longitudinal Localization-Based Cohort Study
Authors: Chen Ming-Chun , Wang Jen-Hung , Chen Jui-Shia , Chang Yung-Chieh , Jan Rong-Hwa , Yang Shang-Hsien , Chu Shao-Yin , Lai Pei-Chun , Chu Chia-Hsiang , Cheng Ching-Feng , Chang Yu-Hsun 
Published: December 2020

Objective:Child hematuria/proteinuria is a risk factor for chronic kidney disease (CKD) in later life, and mass urinary screening could detect asymptomatic glomerulonephritis at an early stage. This study aimed to evaluate the longitudinal prevalence of hematuria/proteinuria and its association with socio-demographic factors among school children in Hualien, Taiwan.Methods:The study cohort consisted of first and fourth graders enrolled from 2008 to 2015 in Hualien. We combined the data from two consecutive health examinations to ensure the validity of the body mass index (BMI), urbanization, proteinuria, and hematuria grouping. Prevalence and health status differences between sex, age, BMI, and urbanization level were examined.Results:A total of 16,990 students within the same BMI and urbanization categories were included during the study interval. The prevalence of persistent hematuria was 1.0%. Fourth graders (odds ratio OR: 1.68,p= 0.002), girls (OR: 1.48,p= 0.014), and students from suburban/rural areas (OR: 1.99, and OR: 4.93, respectively; bothp&lt; 0.001) demonstrated higher hematuria risk. The prevalence of proteinuria was 0.2%. Fourth graders (OR: 4.44,p&lt; 0.001) and students in suburban areas (OR: 0.27,p= 0.031) were associated with persistent proteinuria. After stratifying by age, the significant association remained. A higher risk of proteinuria was noted in underweight subjects (OR: 2.52,p= 0.023) among the fourth-grade students.Conclusion:The prevalence of hematuria/proteinuria in Hualien was higher than the average reported for Taiwan. Hematuria/proteinuria was significantly associated with sex, age, BMI, and urbanization. Our longitudinal results can provide information for future pediatric CKD prevention in Taiwan.
Salidroside Attenuates Cognitive Dysfunction in Senescence-Accelerated Mouse Prone 8 (SAMP8) Mice and Modulates Inflammation of the Gut-Brain Axis
Authors: Xie Zeping , Lu Hui , Yang Sixia , Zeng Yi , Li Wei , Wang Linlin , Luo Guanfeng , Fang Fang , Zeng Ting , Cheng Weidong 
Published: December 2020

Background: Alzheimer’s disease (AD) is a fatal neurodegenerative disease characterized by progressive cognitive decline and memory loss. However, several therapeutic approaches have shown unsatisfactory outcomes in the clinical setting. Thus, developing alternative therapies for the prevention and treatment of AD is critical. Salidroside (SAL) is critical, an herb-derived phenylpropanoid glycoside compound, has been shown to attenuate lipopolysaccharide (LPS)-induced cognitive impairment. However, the mechanism underlying its neuroprotective effects remains unclear. Here, we show that SAL has a therapeutic effect in the senescence-accelerated mouse prone 8 (SAMP8) strain, a reliable and stable mouse model of AD.Methods: SAMP8 mice were treated with SAL, donepezil (DNP) or saline, and cognitive behavioral impairments were assessed using the Morris water maze (MWM), Y maze, and open field test (OFT). Fecal samples were collected and analyzed by 16S rRNA sequencing on an Illumina MiSeq system. Brain samples were analyzed to detect beta-amyloid (Aβ) 1–42 (Aβ1-42) deposition by immunohistochemistry (IHC) and western blotting. The activation of microglia and neuroinflammatory cytokines was detected by immunofluorescence (IF), western blotting and qPCR. Serum was analyzed by a Mouse High Sensitivity T Cell Magnetic Bead Panel on a Luminex-MAGPIX multiplex immunoassay system.Results: Our results suggest that SAL effectively alleviated hippocampus-dependent memory impairment in the SAMP8 mice. SAL significantly 1) reduced toxic Aβ1-42 deposition; 2) reduced microglial activation and attenuated the levels of the proinflammatory factors IL-1β, IL-6, and TNF-α in the brain; 3) improved the gut barrier integrity and modified the gut microbiota (reversed the ratio of Bacteroidetes to Firmicutes and eliminated Clostridiales and Streptococcaceae, which may be associated with cognitive deficits); and 4) decreased the levels of proinflammatory cytokines, particularly IL-1α, IL-6, IL-17A and IL-12, in the peripheral circulation, as determined by a multiplex immunoassay.Conclusion: In summary, SAL reversed AD-related changes in SAMP8 mice, potentially by regulating the microbiota-gut-brain axis and modulating inflammation in both the peripheral circulation and central nervous system. Our results strongly suggest that SAL has a preventive effect on cognition-related changes in SAMP8 mice and highlight its value as a potential agent for drug development.